Enhanced flexibility neurovascular catheter

ABSTRACT

A catheter is provided, such as for distal neurovascular access or aspiration. The catheter includes an elongate flexible body, having a proximal end, a distal end and a side wall defining a central lumen. A distal zone of the side wall includes a tubular inner liner, a tie layer separated from the lumen by the inner liner, a helical coil surrounding the tie layer, adjacent windings of the coil spaced progressively further apart in the distal direction. An outer jacket surrounds the helical coil. The outer jacket is formed from a plurality of tubular segments positioned end to end, coaxially about the coil. The flexural load profile of the catheter as a function of catheter length is configured to provide enhanced distal flexibility while maintaining high backup support.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.62/299,418, filed Feb. 24, 2016, and U.S. Provisional Application No.62/443,595, filed Jan. 6, 2017, the entirety of these applications arehereby incorporated by reference herein.

BACKGROUND OF THE INVENTION

Stroke is the third most common cause of death in the United States andthe most disabling neurologic disorder. Approximately 700,000 patientssuffer from stroke annually. Stroke is a syndrome characterized by theacute onset of a neurological deficit that persists for at least 24hours, reflecting focal involvement of the central nervous system, andis the result of a disturbance of the cerebral circulation. Itsincidence increases with age. Risk factors for stroke include systolicor diastolic hypertension, hypercholesterolemia, cigarette smoking,heavy alcohol consumption, and oral contraceptive use.

Hemorrhagic stroke accounts for 20% of the annual stroke population.Hemorrhagic stroke often occurs due to rupture of an aneurysm orarteriovenous malformation bleeding into the brain tissue, resulting incerebral infarction. The remaining 80% of the stroke population areischemic strokes and are caused by occluded vessels that deprive thebrain of oxygen-carrying blood. Ischemic strokes are often caused byemboli or pieces of thrombotic tissue that have dislodged from otherbody sites or from the cerebral vessels themselves to occlude in thenarrow cerebral arteries more distally. When a patient presents withneurological symptoms and signs which resolve completely within 1 hour,the term transient ischemic attack (TIA) is used. Etiologically, TIA andstroke share the same pathophysiologic mechanisms and thus represent acontinuum based on persistence of symptoms and extent of ischemicinsult.

Emboli occasionally form around the valves of the heart or in the leftatrial appendage during periods of irregular heart rhythm and then aredislodged and follow the blood flow into the distal regions of the body.Those emboli can pass to the brain and cause an embolic stroke. As willbe discussed below, many such occlusions occur in the middle cerebralartery (MCA), although such is not the only site where emboli come torest.

When a patient presents with neurological deficit, a diagnostichypothesis for the cause of stroke can be generated based on thepatient's history, a review of stroke risk factors, and a neurologicexamination. If an ischemic event is suspected, a clinician cantentatively assess whether the patient has a cardiogenic source ofemboli, large artery extracranial or intracranial disease, small arteryintraparenchymal disease, or a hematologic or other systemic disorder. Ahead CT scan is often performed to determine whether the patient hassuffered an ischemic or hemorrhagic insult. Blood would be present onthe CT scan in subarachnoid hemorrhage, intraparenchymal hematoma, orintraventricular hemorrhage.

Traditionally, emergent management of acute ischemic stroke consistedmainly of general supportive care, e.g. hydration, monitoringneurological status, blood pressure control, and/or anti-platelet oranti-coagulation therapy. In 1996, the Food and Drug Administrationapproved the use of Genentech Inc.'s thrombolytic drug, tissueplasminogen activator (t-PA) or Activase®, for treating acute stroke. Arandomized, double-blind trial, the National Institute of NeurologicalDisorders and t-PA Stroke Study, revealed a statistically significantimprovement in stoke scale scores at 24 hours in the group of patientsreceiving intravenous t-PA within 3 hours of the onset of an ischemicstroke. Since the approval of t-PA, an emergency room physician could,for the first time, offer a stroke patient an effective treatmentbesides supportive care.

However, treatment with systemic t-PA is associated with increased riskof intracerebral hemorrhage and other hemorrhagic complications.Patients treated with t-PA were more likely to sustain a symptomaticintracerebral hemorrhage during the first 36 hours of treatment. Thefrequency of symptomatic hemorrhage increases when t-PA is administeredbeyond 3 hours from the onset of a stroke. Besides the time constraintin using t-PA in acute ischemic stroke, other contraindications includethe following: if the patient has had a previous stroke or serious headtrauma in the preceding 3 months, if the patient has a systolic bloodpressure above 185 mm Hg or diastolic blood pressure above 110 mmHg, ifthe patient requires aggressive treatment to reduce the blood pressureto the specified limits, if the patient is taking anticoagulants or hasa propensity to hemorrhage, and/or if the patient has had a recentinvasive surgical procedure. Therefore, only a small percentage ofselected stroke patients are qualified to receive t-PA.

Obstructive emboli have also been mechanically removed from varioussites in the vasculature for years. Mechanical therapies have involvedcapturing and removing the clot, dissolving the clot, disrupting andsuctioning the clot, and/or creating a flow channel through the clot.One of the first mechanical devices developed for stroke treatment isthe MERCI Retriever System (Concentric Medical, Redwood City, Calif.). Aballoon-tipped guide catheter is used to access the internal carotidartery (ICA) from the femoral artery. A microcatheter is placed throughthe guide catheter and used to deliver the coil-tipped retriever acrossthe clot and is then pulled back to deploy the retriever around theclot. The microcatheter and retriever are then pulled back, with thegoal of pulling the clot, into the balloon guide catheter while theballoon is inflated and a syringe is connected to the balloon guidecatheter to aspirate the guide catheter during clot retrieval. Thisdevice has had initially positive results as compared to thrombolytictherapy alone.

Other thrombectomy devices utilize expandable cages, baskets, or snaresto capture and retrieve clot. Temporary stents, sometimes referred to asstentrievers or revascularization devices, are utilized to remove orretrieve clot as well as restore flow to the vessel. A series of devicesusing active laser or ultrasound energy to break up the clot have alsobeen utilized. Other active energy devices have been used in conjunctionwith intra-arterial thrombolytic infusion to accelerate the dissolutionof the thrombus. Many of these devices are used in conjunction withaspiration to aid in the removal of the clot and reduce the risk ofemboli. Suctioning of the clot has also been used with single-lumencatheters and syringes or aspiration pumps, with or without adjunctdisruption of the clot. Devices which apply powered fluid vortices incombination with suction have been utilized to improve the efficacy ofthis method of thrombectomy. Finally, balloons or stents have been usedto create a patent lumen through the clot when clot removal ordissolution was not possible.

Notwithstanding the foregoing, there remains a need for new devices andmethods for treating vasculature occlusions in the body, including acuteischemic stroke and occlusive cerebrovascular disease.

SUMMARY OF THE INVENTION

In accordance with one aspect, there is provided an enhanced flexibilityneurovascular catheter, comprising: an elongate flexible body, having aproximal end, a distal end and a side wall defining a central lumen, adistal zone of the side wall comprising: a tubular inner liner; a softtie layer separated from the lumen by the inner liner; a helical coilsurrounding the tie layer, adjacent windings of the coil spacedprogressively further apart in the distal direction; and an outer jacketsurrounding the helical coil, the outer jacket formed from a pluralityof tubular segments positioned coaxially about the coil; wherein aproximal one of the tubular segments has a durometer of at least about60 D and a distal one of the tubular segments has a durometer of no morethan about 35 D. In one aspect of present disclosure, the tubular lineris formed by dip coating a removable mandrel. In another aspect ofpresent disclosure, the tubular liner comprises PTFE.

In yet another aspect of present disclosure, the tie layer comprisespolyurethane. The tie layer may have a wall thickness of no more thanabout 0.005 inches and may extend along at least the most distal 20 cmof the flexible body. In one aspect of present disclosure, the coilcomprises a shape memory material. The coil may comprise Nitinol, andthe Nitinol may comprise an Austenite state at body temperature.

In one aspect of present disclosure, the outer jacket is formed from atleast five discrete tubular segments. The outer jacket may be formedfrom at least nine discrete tubular segments. The difference indurometer between a proximal one of the tubular segments and a distalone of the tubular segments may be at least about 20 D. The differencein durometer between a proximal one of the tubular segments and a distalone of the tubular segments may be at least about 30 D.

In another aspect of present disclosure, the enhanced flexibilityneurovascular catheter, further comprises a tension support forincreasing the tension resistance in the distal zone. The tensionsupport may comprise a filament and may comprise an axially extendingfilament. The axially extending filament may be carried between theinner liner and the helical coil. The axially extending filament mayincrease the tensile strength to at least about 5 pounds.

Any feature, structure, or step disclosed herein can be replaced with orcombined with any other feature, structure, or step disclosed herein, oromitted. Further, for purposes of summarizing the disclosure, certainaspects, advantages, and features of the embodiments have been describedherein. It is to be understood that not necessarily any or all suchadvantages are achieved in accordance with any particular embodimentdisclosed herein. No individual aspects of this disclosure are essentialor indispensable. Further features and advantages of the embodimentswill become apparent to those of skill in the art in view of theDetailed Description which follows when considered together with theattached drawings and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side elevational schematic view of an intracranialaspiration catheter in accordance with the present invention, with adistal segment in a proximally retracted configuration.

FIG. 2 is a side elevational view as in FIG. 1, with the distal segmentin a distally extended configuration.

FIGS. 3A-3B are cross-sectional elevational views of a distal end ofcatheter 10, with the distal section 34 fully extended.

FIGS. 4A-4C schematically illustrate different cutting tipconfigurations.

FIGS. 4D-4E and 4J-4K schematically illustrate a distal dynamic funneltip configuration.

FIGS. 4F-4G illustrate a dynamic flared tip having a first restraintsystem.

FIGS. 4H-4I illustrate a dynamic flared tip having an alternativerestraint system.

FIG. 5 depicts cerebral arterial vasculature including the Circle ofWillis, and an access catheter positioned at an occlusion in the leftcarotid siphon artery.

FIGS. 6 through 9 show a sequence of steps involved in positioning ofthe catheter and aspirating obstructive material from the middlecerebral artery.

FIG. 10 illustrates removal of the catheter following aspiration ofobstructive material.

FIGS. 11A-11F depict a sequence of steps to access a neurovascularocclusion for aspiration.

FIGS. 12A-12F depict an alternative sequence of steps in accordance withan aspect of the present invention involved in accessing a neurovascularocclusion for aspiration.

FIG. 13 illustrates an aspiration system configured to apply pulsatilenegative pressure through the aspiration catheter.

FIG. 14 illustrates an alternative aspiration system configured to applypulsatile negative pressure through the aspiration catheter.

FIG. 15 illustrates a further alternative aspiration system configuredto apply mechanical vibration through the aspiration catheter.

FIGS. 16 and 17 illustrate a further alternative aspiration systemconfigured to apply mechanical vibration through the aspirationcatheter.

FIG. 18 illustrates a further alternative aspiration system having anagitator configured to apply mechanical vibration at a vibration zone onthe aspiration catheter.

FIG. 19 depicts a simplified agitator such as a hypo tube supported wireplaced in a catheter to create a vibration zone.

FIGS. 20A-20C depict agitators with various distal tip configurations.

FIGS. 20D-20E depict an agitator positioned within a swellable polymerdistal funnel tip.

FIGS. 21A-21B illustrate a moving or wiggling distal tip of a catheterin response to activating the agitator.

FIGS. 22A-22B illustrate media injection from a moving or wigglingdistal tip of an agitator.

FIGS. 23A-23B illustrate media injection from a distal tip of anagitator to assist aspiration.

FIG. 24 depicts a proximal aspiration port carried by a catheter.

FIGS. 25A-25C depict a pulsed aspiration cycle according to anembodiment.

FIG. 26 depicts a perspective view of a rotating hemostasis valve and aproximal drive assembly.

FIG. 27A illustrates a longitudinal cross-sectional elevational viewtaken along the line 27A-27A in FIG. 26.

FIG. 27B illustrates an enlarged longitudinal cross-sectionalelevational view of the proximal drive assembly 2602 from FIG. 27A.

FIG. 28 depicts a cross-sectional perspective view of the proximalportion of FIG. 26.

FIG. 29 depicts a perspective view of an agitator driver, a proximaldrive assembly, and a rotating hemostasis valve.

FIG. 30 illustrates a cross-sectional elevational view of a catheterwall according to an embodiment.

FIG. 31A illustrates a cross-sectional elevational view of a catheterwall according to another embodiment, showing one or more axiallyextending filaments.

FIG. 31B describes a side elevational view of the catheter of FIG. 31A

FIG. 31C illustrates a cross-sectional view taken along the line C-C ofFIG. 31B, showing one or more axially extending filaments.

FIG. 32A depicts a side elevational view of a catheter according to oneembodiment.

FIG. 32B describes a cross-sectional elevational view taken along theline A-A of FIG. 32A.

FIG. 32C illustrates a cross-sectional view taken along the line B-B ofFIG. 32A.

FIG. 33A depicts a side elevational view of a catheter according toanother embodiment.

FIG. 33B describes a cross-sectional elevational view taken along theline A-A of FIG. 33A, showing one or more axially extending filaments.

FIG. 33C illustrates a cross-sectional view taken along the line B-B ofFIG. 33A, showing one or more axially extending filaments.

FIG. 34A illustrates a side elevational view of a progressively enhancedflexibility catheter according to an embodiment.

FIG. 34B is a proximal end view of the enhanced flexibility catheter ofFIG. 34A.

FIG. 35 illustrates back-up support of the catheter in accordance withthe present invention.

FIG. 36 depicts a graph of modulus or durometer of the catheter alongthe length of the catheter, from the proximal end to the distal end.

FIG. 37 depicts a graph of flexure test profiles of catheters inaccordance with the present invention compared with conventionalcatheters.

FIG. 38 is a side elevational schematic view of a transformable catheterin accordance with the present invention.

FIG. 39 is a cross-sectional view taken along the lines 18-18 of FIG.38, showing heating elements within the catheter sidewall.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Referring to FIG. 1, there is disclosed a catheter 10 in accordance withone aspect of the present invention. Although primarily described in thecontext of an axially extendable distal segment aspiration catheter witha single central lumen, catheters of the present invention can readilybe modified to incorporate additional structures, such as permanent orremovable column strength enhancing mandrels, two or more lumen such asto permit drug, contrast or irrigant infusion or to supply inflationmedia to an inflatable balloon carried by the catheter, or combinationsof these features, as will be readily apparent to one of skill in theart in view of the disclosure herein. In addition, the present inventionwill be described primarily in the context of removing obstructivematerial from remote vasculature in the brain, but has applicability asan access catheter for delivery and removal of any of a variety ofdiagnostics or therapeutic devices with or without aspiration.

The catheters disclosed herein may readily be adapted for use throughoutthe body wherever it may be desirable to distally advance a low profiledistal catheter segment from a larger diameter proximal segment. Forexample, axially extendable catheter shafts in accordance with thepresent invention may be dimensioned for use throughout the coronary andperipheral vasculature, the gastrointestinal tract, the urethra,ureters, Fallopian tubes and other lumens and potential lumens, as well.The telescoping structure of the present invention may also be used toprovide minimally invasive percutaneous tissue access, such as fordiagnostic or therapeutic access to a solid tissue target (e.g., breastor liver or brain biopsy or tissue excision), delivery of laparoscopictools or access to bones such as the spine for delivery of screws, bonecement or other tools or implants.

The catheter 10 generally comprises an elongate tubular body 16extending between a proximal end 12 and a distal functional end 14. Thelength of the tubular body 16 depends upon the desired application. Forexample, lengths in the area of from about 120 cm to about 140 cm ormore are typical for use in femoral access percutaneous transluminalcoronary applications. Intracranial or other applications may call for adifferent catheter shaft length depending upon the vascular access site,as will be understood in the art.

In the illustrated embodiment, the tubular body 16 is divided into atleast a fixed proximal section 33 and an axially extendable andretractable distal section 34 separated at a transition 32.

Referring to FIGS. 3A and 3B, there is illustrated a cross-sectionalview of the distal segment 34 shown extended distally from the proximalsegment 33 in accordance with the present invention. Distal segment 34extends between a proximal end 36 and a distal end 38 and defines atleast one elongate central lumen 40 extending axially therethrough.Distal end 38 may be provided with one or more movable side walls orjaws 39, which move laterally in the direction of an opposing side wallor jaw 41 under the influence of aspiration, to enable the distal end 38to bite or break thrombus or other material into smaller particles, tofacilitate aspiration through lumen 40. Both walls 39 and 41 may bemovable towards and away from each other to break up thrombus as isdiscussed further below. For certain applications, the proximal section33 may also or alternatively be provided with one or two opposing jaws,also responsive to vacuum or mechanical actuation to break up thrombus.

The inner diameter of the distal section 34 may be between about 0.030inches and about 0.112 inches, between about 0.040 inches and about0.102 inches, between about 0.045 inches and about 0.097 inches, betweenabout 0.050 inches and about 0.092 inches, between about 0.055 inchesand about 0.087 inches, between about 0.060 inches and about 0.082inches, between about 0.062 inches and about 0.080 inches, between about0.064 inches and about 0.078 inches, between about 0.066 inches andabout 0.076 inches, between about 0.068 inches and about 0.074 inches,or between about 0.070 inches and about 0.072 inches.

The inner diameter and the outer diameter of the distal section 34 maybe constant or substantially constant along its longitudinal length.Alternatively, the distal section 34 may be tapered near its distal end.The distal section 34 may be tapered at less than or equal to about 5cm, about 10 cm, about 15 cm, about 20 cm, about 23 cm, about 25 cm,about 30 cm, about 31 cm, about 35 cm, about 40 cm, about 45 cm, about50 cm, about 60 cm, or about 70 cm from its distal end.

The inner diameter of the distal section 34 may be tapered or decreasednear the distal end by less than or equal to about 95%, about 90%, about85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%,about 50%, about 45%, about 40%, about 35%, about 30%, about 25%, about20%, about 10%, or about 5%. The inner diameter of the distal section 34may be tapered or decreased near the distal end by greater than or equalto about 95%, about 90%, about 85%, about 80%, about 75%, about 70%,about 65%, about 60%, about 55%, about 50%, about 45%, about 40%, about35%, about 30%, about 25%, about 20%, about 10%, or about 5%. Thetapered inner diameter of the distal section 34 may be by less than orequal to about 0.11 inches, about 0.1 inches, about 0.090 inches, about0.080 inches, about 0.070 inches, about 0.065 inches, about 0.060inches, about 0.055 inches, about 0.050 inches, about 0.045 inches,about 0.040 inches, about 0.035 inches, about 0.030 inches, about 0.025inches, about 0.020 inches, about 0.015 inches, or about 0.010 inches.

The length of the distal section 34 may be between about 13 cm and about53 cm, between about 18 cm and about 48 cm, between about 23 cm andabout 43 cm, or between about 28 cm and about 38 cm. The length of thedistal section 34 may be less than or equal to about 20 cm, about 25 cm,about 30 cm, about 33 cm, about 35 cm, about 40 cm, about 41 cm, about45 cm, about 50 cm, about 55 cm, about 60 cm, about 70 cm, or about 80cm. The length of the distal section 34 may depend on the degree oftapering of the internal diameter of the distal section 34.

The proximal end 36 of distal section 34 is provided with a proximallyextending pull wire 42. Pull wire 42 extends proximally throughout thelength of the tubular body 16, to control 24 which may be carried bymanifold 18. Axial movement of control 24 produces a corresponding axialmovement of distal section 34 with respect to proximal section 33 as hasbeen discussed. Alternatively, the proximal end of pull wire 42 may exitthrough a port on manifold 18, such that it may be manually grasped andpulled or pushed by the clinician to extend or retract the distalsection 34. The length of the pull wire 42 may be between about 700 mmand about 1556 mm, between about 800 mm and about 1456 mm, between about850 mm and about 1406 mm, between about 900 mm and about 1356 mm,between about 950 mm and about 1306 mm, between about 1000 mm and about1256 mm, between about 1020 mm and about 1236 mm, between about 1040 mmand about 1216 mm, between about 1060 mm and about 1196 mm, betweenabout 1080 mm and about 1176 mm, between about 1100 mm and about 1156mm, between about 1110 mm and about 1146 mm, or between about 1120 mmand about 1136 mm.

Upon distal advance of pull wire 42 to its limit of travel, an overlap44 remains between the proximal end 36 of distal section 34 and theproximal section 33. This overlap 44 is configured to provide a seal toenable efficient transmission of vacuum from proximal section 33 todistal section 34. Overlap 44 may be provided with any of a variety ofadditional features to facilitate a seal, such as a gasket, coating ortightly toleranced sliding fit. Preferably the clearance between the ODof the distal section 34 and ID of the proximal section 33, at least inthe vicinity of transition 32, will be no more than about 0.005 inchesand preferably no more than about 0.003 inches to provide an effectiveseal in a blood environment.

Following positioning of the distal end of proximal section 33 withinthe vasculature, such as within the cervical carotid artery, the control24 is manipulated to distally advance distal section 34 deeper into thevasculature. For this purpose, the pull wire 42 will be provided withsufficient column strength to enable distal advance of the distal tip 38as will be discussed below.

The pull wire 42 and distal section 34 may be integrated into a catheteras illustrated in FIGS. 1 and 2. Alternatively, distal section 34 andpull wire 42 may be configured as a stand-alone catheter extensiondevice as is discussed in greater detail below. The catheter extensiondevice may be introduced into the proximal end of proximal section 33after placement of proximal section 33 and advanced distally therethrough as illustrated in FIG. 3 A, to telescopically extend the reachof the aspiration system.

Referring to FIG. 3B, the pull wire 42 may comprise a tubular wallhaving an axially extending central lumen 45. The central lumen 45permits introduction of media such as lubricants, drugs, contrast agentsor others into the distal section 34. In addition, the central lumen 45extending through pull wire 42 permits introduction of an agitator as isdiscussed in greater detail below.

Referring to FIGS. 4A through 4C, the distal tip 38 may be provided anyof a variety of structures which produce an active movement such as abiting action in response to the application of an activation force suchas a vacuum in lumen 40. Alternatively, an axially movable control wiremay be connected with respect to a side wall of the distal tip 38, toenable cutting action under positive mechanical force. FIG. 4Aillustrates a distal tip 38 in an open configuration, while FIG. 4Billustrates distal tip 38 with opposing side walls 39 and 41 drawntogether by the negative pressure in aspiration lumen 40. This may beaccomplished by providing a tapered thickness in side walls 39 and 41,or a groove or living hinge which facilitates lateral movement of atleast one of side wall 39 or 41.

Alternatively, referring to FIG. 4C, a pivot point or hinge 43 may beprovided to enable lateral movement of side wall 39 to operate as a jaw.Two opposing side walls may be moveable medially and laterally withbilateral symmetry like a duck bill valve. Three or more jaws may beprovided, such as three triangular jaws separated at about 120° spacingwhich under an aspiration pulse close to form a pyramid closed tip.

In some implementations of the present invention, the distal tip 14 ispreferably provided with the capability to dilate beyond the nominaldiameter of distal section 34. This provides a conical funnel like tipwith an enlarged distal opening, to facilitate introduction ofthrombotic material into the lumen 40. See FIGS. 4D-4K. The diameter atthe distal opening of the fully opened funnel exceeds the diameter of acylindrical extension of the adjacent tubular body by at least about10%, preferably at least about 25% or 45% or more. This may beaccomplished by providing the distal end 14 with an expandable material,or a plurality of laterally movable jaws or petals such as at leastabout three or five or six or more petals that are advanceable radiallyinwardly into a coaptive orientation, and radially outwardly to providea flared inside diameter of aspiration lumen 40 which increases in thedistal direction.

The flexible petals may be retained in a radially inwardly inclinedconfiguration such as by application of negative pressure via lumen 40during transluminal navigation of the distal section 34. Upon removal ofthe negative pressure, the panels may incline radially outwardly inresponse to a preset bias. Application of pulsatile vacuum maythereafter cause the panels to close radially inwardly to perform thebiting function described previously.

The distal funnel opening may be actuated in a variety of other ways aswill be apparent to those of skill in the art, such as by providing apull wire or axially slideable outer or inner sleeve to open and closethe funnel in response to mechanical movement of the wire or sleeve.Alternatively the funnel opening may be controlled by rotation of acontrol wire or tubular sleeve relative to the distal section 34, toactivate an iris or spiral mechanism such as a helical ribbon or wirecarried by the distal tip.

The normal state of the distal funnel may be a cylindricalconfiguration, and a mechanical, thermal or electrical actuator may beutilized to enlarge the distal funnel opening. Alternatively, the normalstate of the funnel may be conical, and a mechanical, thermal orelectrical actuator may be utilized to reduce the diameter such as fortransluminal navigation. The petals or other wall of the funnel orelements disposed within the wall of the funnel may comprise a shapememory material such as a shape memory polymer or metal alloy such asnitinol, which may be laser cut from tube stock or woven into a finemesh. The geometry of the funnel may be transformed by application ofheat, such as body heat, or heat from a heat source carried by thecatheter such as an electrical resistance wire within the wall oradjacent the catheter tip. Heat may alternatively be applied from a heatsource introduced by way of central lumen 40, such as a heated fluid, ora removable heater such as an elongate flexible body carrying aresistance coil. Transformation of the funnel from one configuration tothe other may alternatively be accomplished by reducing the temperatureof the funnel below body temperature such as by introducing a cooledfluid into thermal communication with the funnel tip or providing thecatheter or a removable cooling catheter with a Joule-Thomson expansionchamber located near the distal end.

In an alternate configuration, the sidewall of the funnel is providedwith an inflatable balloon in the form of a ring or hoop, incommunication with an inflation lumen extending throughout the length ofthe catheter. Introduction of inflation media inflates the annularballoon, transforming the configuration of the funnel tip from a reduceddiameter to an enlarged diameter.

In an alternate configuration, the distal tip is biased into the funnelconfiguration, and restrained into a cylindrical configuration such asfor transluminal navigation. When the funnel tip is desired to beenlarged, the restraint can be removed. The restraint may comprise anouter tubular covering membrane or loop configured to be removed bypulling a pull wire in a proximal direction. Alternatively, therestraint may be a bioabsorbable material, which dissolves following apreset amount of time that exceeds the anticipated time from vascularaccess to reach the final intravascular position.

Referring to FIGS. 4J-4K, the distal flared tip may comprise embeddedelastic elements (e.g., a coil, struts or cage) such as spring steel,Nitinol or others known in the art that bias the tip into the flaredconfiguration. The elastic elements such as in the form of a Nitinolcage may alternatively reside on the ID of the catheter. The polymer tiprestrains the elastic elements to provide a cylindrical exteriorconfiguration for transluminal navigation as seen in FIG. 4J. Softeningthe polymer (e.g., a hydrophilic blend) such as by body heat or moistureallows the elastic elements to transform the tip into the funnelconfiguration as seen in FIG. 4K. Alternatively, a conical NiTi cage atthe tip is coated with a double hydrophilic non-cross linked glue. Asthe catheter advances the glue dissolves and gradually flares the tipinto a funnel. The polymer tip may be formed without embedded elasticcomponents and instead comprise a coextrusion with multiple layers,varying thickness in multiple layers, blending hydrophilic components atdifferent ratios to control flaring. Multiple axially extending pullwires may be embedded through extruded lumen extending axiallythroughout the catheter wall. The wires are pushed or pulled toopen/close the catheter distal end to flare or collapse. Funnel-shaped,underexpanded NiTi stent can be deployed at the tip area straddlingbetween high and low durometer regions but greater length into highdurometer region. Once ready to engage a clot, the stent can be pusheddistally further into the low durometer tip. After complete clotretrieval the stent is pulled back into high durometer region,collapsing the funnel. This is an example of an active on-demandfunneling tip.

Referring to FIG. 4F, there is illustrated a cross-sectional view of adistal end of a tubular catheter body such as distal section 34. Thetubular body is provided with a distal tip 38 in the form of a selfexpandable (e.g., NiTinol) mesh 50, constrained by an outer tubularrestraint 52. Restraint 52 may comprise a proximately retractabletubular body extending proximally to a control on the proximal manifold;a peel away sheath carried by an elongate proximally retractable pullwire, or other mechanism disclosed elsewhere herein. As shown in FIG.4G, proximal retraction of tubular restraint 52 with respect to tubularbody 34, or distal advance of tubular body 34 with respect to restraint52 exposes and releases the mesh 50 to self expand to a funnel shape tofacilitate capture and removal of intravascular debris.

Referring to FIGS. 4H and 4I, the self expandable conical mesh 50 isrestrained by interweaving an internal restraint wire 54. Restraint wire54 may be a procedure guide wire, or a dedicated restraint wire.Proximal retraction of the restraint wire 54 releases the mesh 50, toself expanded to a final, funnel configuration. Release of the mesh 50may be accomplished in a variety of alternative ways, such as bioabsorbable materials, and electrolytic detachment.

The proximal end 12 of catheter 10 is additionally provided with amanifold 18 having one or more access ports as is known in the art.Generally, manifold 18 is provided with a proximal port such as aguidewire port 20 in an over-the-wire construction, and at least oneside port such as aspiration port 22. Alternatively, the aspiration port22 may be omitted if the procedure involves removal of the guidewireproximally from the guidewire port 20 following placement of theaspiration catheter, and aspiration through the guidewire port.Additional access ports and lumen may be provided as needed, dependingupon the functional capabilities of the catheter. Manifold 18 may beinjection molded from any of a variety of medical grade plastics, orformed in accordance with other techniques known in the art.

Manifold 18 may additionally be provided with a control 24, forcontrolling the axial position of the distal segment 34 of the catheter.Control 24 may take any of a variety of forms depending upon themechanical structure and desired axial range of travel of the distalsegment 34. In the illustrated embodiment, control 24 comprises a sliderswitch which is mechanically axially movably linked to the distalsegment such that proximal retraction of the slider switch 24 produces aproximal movement of the distal segment 34. This retracts the distalsegment 34 into the proximal section 33 as illustrated in FIG. 1. Distalaxial advancement of the slider switch 24 produces a distal axialadvance of the distal segment 34, as illustrated in FIGS. 2 and 3.

Any of a variety of controls may be utilized, including switches,buttons, levers, rotatable knobs, pull/push wires, and others which willbe apparent to those of skill in the art in view of the disclosureherein. The control will generally be linked to the distal segment by acontrol wire 42.

Alternatively, the proximal section 33 and distal section 34 maybeprovided as separate devices, in which construction the proximal controlmay be omitted. The distal end of proximal section 33 may be providedwith one or more jaws as has been discussed previously herein, formorcellating or otherwise breaking thrombus or other obstruction intopieces or otherwise facilitating aspiration. The proximal section 33 mayadditionally be mechanically coupled to or adapted for coupling to asource of vibrational or rotational movement, such as to provide theintermittent or pulsatile movement discussed elsewhere herein tofacilitate navigation into the vasculature.

Using axial reciprocation, and/or rotation, and/or biting action of thedistal jaws, the clinician may be able to reach the obstruction usingproximal section 33. See, for example, FIG. 5 in which proximal section33 is able to reach an obstruction in the left carotid siphon. If,however, the proximal section 33 is not able to advance sufficientlyclose to the obstruction, a separate telescoping distal section 34 maybe introduced into the proximal section 33 and advanced therethrough andbeyond, as illustrated in FIGS. 2 and 6-10, to reach the obstruction.

The cerebral circulation is regulated in such a way that a constanttotal cerebral blood flow (CBF) is generally maintained under varyingconditions. For example, a reduction in flow to one part of the brain,such as in acute ischemic stroke, may be compensated by an increase inflow to another part, so that CBF to any one region of the brain remainsunchanged. More importantly, when one part of the brain becomes ischemicdue to a vascular occlusion, the brain compensates by increasing bloodflow to the ischemic area through its collateral circulation.

FIG. 5 depicts cerebral arterial vasculature including the Circle ofWillis. Aorta 100 gives rise to right brachiocephalic artery 82, leftcommon carotid artery (CCA) 80, and left subclavian artery 84. Thebrachiocephalic artery 82 further branches into right common carotidartery 85 and right subclavian artery 83. The left CCA gives rise toleft internal carotid artery (ICA) 90 which becomes left middle cerebralartery (MCA) 97 and left anterior cerebral artery (ACA) 99. Anteriorly,the Circle of Willis is formed by the internal carotid arteries, theanterior cerebral arteries, and anterior communicating artery 91 whichconnects the two ACAs. The right and left ICA also send right posteriorcommunicating artery 72 and left posterior communicating artery 95 toconnect, respectively, with right posterior cerebral artery (PCA) 74 andleft PCA 94. The two posterior communicating arteries and PCAs, and theorigin of the posterior cerebral artery from basilar artery 92 completethe circle posteriorly.

When an occlusion occurs acutely, for example, in left carotid siphon70, as depicted in FIG. 5, blood flow in the right cerebral arteries,left external carotid artery 78, right vertebral artery 76 and leftvertebral artery 77 increases, resulting in directional change of flowthrough the Circle of Willis to compensate for the sudden decrease ofblood flow in the left carotid siphon. Specifically, blood flow reversesin right posterior communicating artery 72, right PCA 74, left posteriorcommunicating artery 95. Anterior communicating artery 91 opens,reversing flow in left ACA 99, and flow increases in the left externalcarotid artery, reversing flow along left ophthalmic artery 75, all ofwhich contribute to flow in left ICA 90 distal the occlusion to provideperfusion to the ischemic area distal to the occlusion.

As illustrated in FIG. 5, the proximal segment of catheter 10 istransluminally navigated along or over the guidewire, to the proximalside of the occlusion. Transluminal navigation may be accomplished withthe distal section 34 of the catheter in the first, proximally retractedconfiguration. This enables distal advance of the proximal section 33until further progress is inhibited by small and/or tortuousvasculature. Alternatively, the distal section 34 is a separate device,and is not inserted into the proximal section 33 until it is determinedthat the proximal section 33 cannot safely reach the occlusion. In theexample illustrated in FIG. 5, the occlusion may be safely reached bythe proximal section 33, without the need to insert or distally extend adistal section 34.

The distal end of the proximal section 33 of aspiration catheter 10 isinserted typically through an incision on a peripheral artery over aguidewire and advanced as far as deemed safe into a more distal carotidor intracranial artery, such as the cervical carotid, terminal ICA,carotid siphon, MCA, or ACA. The occlusion site can be localized withcerebral angiogram or IVUS. In emergency situations, the catheter can beinserted directly into the symptomatic carotid artery after localizationof the occlusion with the assistance of IVUS or standard carotid dopplerand TCD.

If it does not appear that sufficient distal navigation of the proximalsection 33 to reach the occlusion can be safely accomplished, the distalsection 34 is inserted into the proximal port 20 and/or distallyextended beyond proximal section 33 until distal tip 38 is positioned inthe vicinity of the proximal edge of the obstruction.

Referring to FIG. 6, an obstruction 70 is lodged in the middle cerebralartery 97. Proximal section 33 is positioned in the ICA and not able tonavigate beyond a certain point such as at the branch 96 to the MCAartery 97. The proximal section 33 may be provided with a distal section34 carried there in. Alternatively, a separate distal section 34 may beintroduced into the proximal end of proximal section 33 once thedetermination has been made that the obstruction 70 cannot be reacheddirectly by proximal section 33 alone. As seen in FIGS. 7 and 8, thedistal section 34 may thereafter be transluminally navigated through thedistal tortuous vasculature between proximal section 33 and theobstruction 70.

Referring to FIG. 9, the obstruction 70 may thereafter be drawn intodistal section 34 upon application of constant or pulsatile negativepressure with or without the use of jaws or other activation on thedistal end of distal section 34 as discussed elsewhere herein. Once theobstruction 70 has either been drawn into distal section 34, or drawnsufficiently into distal section 34 that it may be proximately withdrawnfrom the body, proximal section 33 and distal section 34 are thereafterproximally withdrawn.

Aspiration may be applied via lumen 40, either in a constant mode, or ina pulsatile mode. Preferably, pulsatile application of vacuum will causethe distal tip 38 to open and close like a jaw, which facilitatesreshaping the thrombus or biting or nibbling the thrombus material intostrands or pieces to facilitate proximal withdrawal under negativepressure through lumen 40. Application of aspiration may be accompaniedby distal advance of the distal tip 38 into the thrombotic material.

Pulsatile application of a vacuum may oscillate between positive vacuumand zero vacuum, or between a first lower negative pressure and a secondhigher negative pressure. Alternatively, a slight positive pressure maybe alternated with a negative pressure, with the application of negativepressure dominating to provide a net aspiration through the lumen 40.Pulse cycling is discussed in greater detail in connection with FIG. 25.

The proximal manifold and/or a proximal control unit (not illustrated)connected to the manifold may enable the clinician to adjust any of avariety of pulse parameters including pulse rate, pulse duration, timingbetween pulses as well as the intensity of the pulsatile vacuum.

The distal section may thereafter be proximally retracted into proximalsection 33 and the catheter proximally retracted from the patient.Alternatively, proximal retraction of the catheter 10 may beaccomplished with the distal section 34 in the distally extendedposition. A vasodilator, e.g., nifedipine or nitroprusside, may beinjected through a second lumen to inhibit vascular spasm induced as aresult of instrumentation.

Pressure may be monitored by a manometer carried by the catheter or awire positioned in a lumen of the catheter. A pressure control anddisplay may be included in the proximal control unit or proximal end ofthe catheter, allowing suction within the vessel to be regulated.

Focal hypothermia, which has been shown to be neuroprotective, can beadministered by perfusing hypothermic oxygenated blood or fluid.Moderate hypothermia, at approximately 32 to 34° C., can be introducedduring the fluid infusion. Perfusion through a port on manifold 18 canbe achieved by withdrawing venous blood from a peripheral vein andprocessing through a pump oxygenator, or by withdrawing oxygenated bloodfrom a peripheral artery, such as a femoral artery, and pumping it backinto the carotid artery.

If continuous and/or intermittent suction fails to dislodge theocclusion, a thrombolytic agent, e.g., t-PA, can be infused throughcentral lumen 40 or a second lumen to lyse any thrombotic material withgreater local efficacy and fewer systemic complications. Administrationof thrombolytic agent, however, may not be recommended for devices whichare inserted directly into the carotid artery due to increased risk ofhemorrhage.

The intensity of intermittent or pulsatile vacuum applied to lumen 40may be adjusted to cause the distal tip 38 of the catheter 10 toexperience an axial reciprocation or water hammer effect, which canfurther facilitate both translumenal navigation as well as dislodging orbreaking up the obstruction. Water hammer, or more generally fluidhammer, is a pressure surge or wave caused when a fluid in motion isforced to stop or change direction suddenly, creating a momentum change.A water hammer commonly occurs when a valve closes suddenly at the endof a pipeline system, and a pressure wave propagates in the pipe. Apressure surge or wave is generated inside the lumen 40 of theaspiration catheter 10 when a solenoid or valve closes and stops thefluid flow suddenly, or other pulse generator is activated. As thepressure wave propagates in the catheter 10, it causes the catheter 10to axially vibrate. Since vibration can reduce surface friction betweenthe outer diameter of the catheter 10 and the inner diameter of thevessel wall, it enables catheter to track through tortuous anatomies aswell as assist capturing thrombus.

Referring to FIGS. 11A-11F, the cerebral circulation 1100 is simplifiedfor the ease of demonstrating procedural steps. A thrombotic occlusion1102 is in the right middle cerebral artery (RMCA) 1104. The RMCA 1104branches from the right internal carotid artery (RICA) 1106. The RICA1106 branches from the right common carotid artery (RCCA) (not shown).The RICA 1106 comprises cerebral 1108 (most distal from the aorta 100),cavernous 1110, and petrous 1112 (most proximal from the aorta 100)segments. The RCCA branches from the brachiocephalic artery. Thebrachiocephalic artery branches from the arch 1114 of the aorta 100.

The procedural steps for aspirating a thrombotic occlusion are describedas follows. Referring to FIG. 11A, an introducer sheath 1120 isintroduced at the femoral artery 1118. The outer diameter of theintroducer sheath 1120 may be equal to or less than about 12 F, 11 F, 10F, 9 F, 8 F, 7 F, or 6 F. Then, a guide sheath 1122 is inserted throughthe introducer sheath 1120. The outer diameter of the guide sheath 1122may be equal to or less than about 9 F, 8 F, 7 F, 6 F, 5 F, 4 F, or 3 F,and the inner diameter of the introducer sheath 1120 may be greater thanthe outer diameter of the guide sheath 1122.

Referring to FIG. 11B, an insert catheter 1124 is inserted through theguide sheath 1122. The outer diameter of the insert catheter 1124 may beequal to or less than about 9 F, 8 F, 7 F, 6 F, 5 F, 4 F, or 3 F, andthe inner diameter of the guide sheath 1122 may be greater than theouter diameter of the insert catheter 1124. In some cases, a firstguidewire 1126 may be introduced through the insert catheter 1124 (notshown in FIG. 11B). Then, the guide sheath 1122, the insert catheter1124, and optionally the first guidewire 1126 are tracked up to theaortic arch 1114. The insert catheter 1124 is used to engage the originof a vessel. In FIG. 11B, the insert catheter 1124 engages the origin1116 of the brachiocephalic artery 82. An angiographic run is performedby injecting contrast media through the insert catheter 1124. In thecases where the first guidewire 1126 is used before the angiographicrun, the first guidewire 1126 is removed prior to injecting the contrastmedia.

Referring to FIG. 11C, the first guidewire 1126 is inserted through thelumen of the insert catheter 1124. Then, the first guidewire 1126, theinsert catheter 1124, and the guide sheath 1122 are advanced together tothe ICA 1106. Referring to FIG. 11D, due to the stiffness of a typicalguide sheath 1122 currently available in the market (e.g., Neuron MAXSystem produced by Penumbra Inc.), the most distal vessel that the guidesheath 1122 could navigate to is the petrous segment 1112 of the ICA1106. Once the first guidewire 1126, the insert catheter 1124, and theguide sheath 1122 are advanced to the ICA 1106, both the first guidewire1126 and the insert catheter 1124 are removed.

Referring to FIG. 11E, a second guidewire 1132 loaded inside the centrallumen of a reperfusion catheter 1130 (e.g., 3Max), which is loadedinside the central lumen of an aspiration catheter 1128 (e.g., ACE 68),are introduced through the guide sheath 1122. The diameter of the secondguidewire 1132 may be equal to or less than about 0.03″, about 0.025″,about 0.02″, about 0.016″, about 0.014″, about 0.01″, or about 0.005″.The inner diameter of the reperfusion catheter 1130 may be greater thanthe outer diameter of the second guidewire 1132. The inner diameter ofthe aspiration catheter 1128 may be greater than the outer diameter ofthe reperfusion catheter 1130. The inner diameter of the guide sheath1122 may be greater than the outer diameter of the aspiration catheter1128. Then, the second guidewire 1132 is advanced distally andpositioned at the proximal end of the clot 1102 in the MCA 1104.

Referring to FIG. 11F, the aspiration catheter 1128 is tracked over thereperfusion catheter 1130 and the second guidewire 1132 to the proximalend of the clot 1102 in the MCA 1104. Both the second guidewire 1132 andthe reperfusion catheter 1130 are removed. A vacuum pressure is thenapplied at the proximal end of the aspiration catheter 1128 to aspiratethe clot 1102 through the central lumen of the aspiration catheter 1128.

A preferable, simplified method for aspirating a thrombotic occlusion inaccordance with the present invention is described in connection withFIGS. 12A-12F. The alternative steps for aspirating a thromboticocclusion make use of a transitional guidewire and a transitional guidesheath. The transitional guidewire has a soft and trackable distalsegment with a smaller diameter so that the transitional guidewire maybe advanced deeper than the guidewire 1126 described in FIG. 11C. Inaddition, the transitional guide sheath has a soft and trackable distalsegment such that the transitional guide sheath may be advanced deeperthan the guide sheath 1122 described in FIG. 11D. Using a transitionalguidewire and a transitional guide sheath that can be advanced to anarea near the clot eliminates the need to use a second guidewire or areperfusion catheter to reach the clot.

Referring to FIG. 12A, an introducer sheath 1220 is introduced at thefemoral artery 1218. The outer diameter of the introducer sheath 1220may be equal to or less than about 12 F, 11 F, 10 F, 9 F, 8 F, 7 F, or 6F. Then, a transitional guide sheath 1222 such as the combination accessand aspiration catheter discussed in greater detail below is insertedthrough the introducer sheath 1120 at the femoral artery 1218. The outerdiameter of the guide sheath 1222 may be equal to or less than about 9F, 8 F, 7 F, 6 F, 5 F, 4 F, or 3 F. Referring to FIG. 12B, an insertcatheter 1224 is inserted through the transitional guide sheath 1222.The outer diameter of the insert catheter 1224 may be less than about 9F, 8 F, 7 F, 6 F, 5 F, 4 F, or 3 F, and the inner diameter of thetransitional guide sheath 1222 may be greater than the outer diameter ofthe insert catheter 1224. In some cases, a first guidewire may beintroduced through the insert catheter 1224 (not shown in FIG. 12B). Thediameter of the proximal section of the first guidewire may be equal toor less than about 0.079″, about 0.066″, about 0.053″, about 0.038″,about 0.035″, about 0.030″, or about 0.013″.

The transitional guide sheath 1222, the insert catheter 1224, andoptionally the first guidewire are tracked up to the aortic arch 1214.See FIG. 12B. The insert catheter 1224 may be used to select the originof a vessel. In FIG. 12B, the insert catheter 1224 engages the origin1216 of the brachiocephalic artery 82. An angiographic run may beperformed by injecting contrast media through the insert catheter 1224.In the cases where the first guidewire is used before the angiographicrun, the first guidewire is preferably removed prior to injecting thecontrast media.

Referring to FIG. 12C, the transitional guidewire 1226 is insertedthrough the lumen of the insert catheter 1224 or guide sheath 1222. Thediameter of at least a portion of the transitional guidewire 1226 (e.g.,proximal diameter) is substantially similar to that of the firstguidewire 1126. The diameter of at least a portion of the transitionalguidewire 1226 (e.g., distal diameter) may be smaller than that of thefirst guidewire 1126 and may have a diameter along a proximal segment ofat least about 0.030″ and in one implementation about 0.038″. Atransition begins within the range of from about 15 cm-30 cm from thedistal end, and typically no more than about 20 cm or 25 cm from thedistal end, distally of which the diameter tapers down to no more thanabout 0.018″ and in one implementation about 0.016″. Referring to FIG.12D, if utilized, the insert catheter 1224 may be removed because it istoo stiff to be advanced to the MCA 1204. In certain implementations ofthe invention, the transitional guidewire 1226 provides sufficient backup support that the combination access and aspiration catheter 1224 maybe advanced directly over the transitional guidewire without anyintervening devices. Then, the transitional guidewire 1226 is advancedto the MCA 1204. The transitional guidewire 1226 has a distal segmentthat has a smaller diameter than that of the first guidewire 1126described in FIG. 11C. The distal segment of the transitional guidewire1226 comprises a soft and atraumatic tip and can be tracked to theremote neurovasculature such as the MCA 1204, which is distal to thepetrous segment 1212 of the ICA 1206.

Referring to FIG. 12E, the transitional guide sheath 1222 is advanced toor beyond the cavernous segment 1210 or the cerebral 1208 segment of theICA 1206. Unlike the guide sheath 1122 described in FIG. 11D, thetransitional guide sheath 1222 may be advanced to the cavernous segment1210 or the cerebral 1208 segment of the ICA 1206 beyond the petroussegment 1212 because the transitional guide sheath 1222 has a soft yettrackable distal segment described in further detail below, for examplein connection with FIG. 30. The larger proximal diameter and stifferbody of the transitional guidewire 1226 may provide better support forthe transitional guide sheath 1222 to track through the vasculature.

Referring to FIG. 12F, after the transitional guide sheath 1222 isadvanced to the cerebral segment 1208 of the ICA 1206, the transitionalguidewire 1226 is removed. Then, a vacuum pressure is applied at theproximal end of the transitional guide sheath 1222 to aspirate the clot1202 through the central lumen of the transitional guide sheath 1222.The inner diameter of the transitional guide sheath 1222 may be equal toabout or greater than about 0.100″, about 0.088″, about 0.080″, about0.070″, or about 0.060″. The inner diameter of the transitional guidesheath 1222 is larger than the aspiration catheter 1128 described inFIG. 11E, which translates to more effective aspiration. Thecross-sectional area of the central lumen of the transitional guidesheath 1222 may be almost twice as large as that of the largestaspiration catheter 1128 currently available.

If the guide sheath 1222 is not able to track deep enough into thedistal vasculature to reach the clot or other desired target site, atelescopic extension segment as discussed elsewhere herein may beintroduced into the proximal end of sheath 1222 and advanced distally toextend beyond the distal end of the sheath 1222 and thereby extend thereach of the aspiration system. In one implementation of the invention,the extension segment has an ID of about 0.070″.

If thrombotic material is not able to be drawn into the sheath 1222 orextension segment under constant vacuum, pulsatile vacuum may be appliedas discussed below. If pulsatile vacuum does not satisfactorily capturethe clot, an agitator may be advanced through the sheath 1222 andextension segment to facilitate drawing the clot into the central lumen.Additional details of the agitator and its use are disclosed below.

A pulsatile vacuum pressure aspirator may be used in order to improveeffectiveness of aspiration for vascular thrombectomy and to improvecatheter trackability through tortuous vasculatures. FIG. 13 shows anembodiment of a pulsatile vacuum pressure aspirator 300 that appliesintermittent or pulsatile vacuum to lumen 40. In the illustratedembodiment, the pulsatile vacuum pressure aspirator 300 is in fluidconnection with the proximal end 12 of the catheter 10 and comprisesvacuum generator 302, vacuum chamber 310, collection canister 312,solenoid valve 314, frequency modulator 316, valve controller 318, andremote controller 320.

Vacuum generator 302 comprises a vacuum pump 304, a vacuum gauge 306,and a pressure adjustment control 308. The vacuum pump 304 generatesvacuum. The vacuum gauge 306 is in fluid connection with the vacuum pump304 and indicates the vacuum pressure generated by the pump 304. Thepressure adjustment control 308 allows the user to set to a specificvacuum pressure. Any of a variety of controls may be utilized, includingswitches, buttons, levers, rotatable knobs, and others which will beapparent to those of skill in the art in view of the disclosure herein.

Vacuum chamber 310 is in fluid connection with the vacuum generator 302and acts as a pressure reservoir and/or damper. Collection canister 312is in fluid connection with the vacuum chamber 310 and collects debris.The collection canister 312 may be a removable vial that collects debrisor tissues, which may be used for pathologic diagnosis. Vacuum chamber310 and collection canister 312 may be separate components that are influid connection with each other or a merged component. In theillustrated embodiment, the vacuum chamber 310 and the collectioncanister 312 is a merged component and is in fluid connection with thevacuum generator 302.

Solenoid valve 314 is located in the fluid connection path between aluer or other connector configured to releasably connect to an accessport of the catheter 10 and the vacuum chamber 310/collection canister312. The solenoid valve 314 controls the fluid flow from the catheter 10to the vacuum chamber 310/collection canister 312.

Pulsatile vacuum pressure aspirator 300 may comprise frequency modulator316 for control of the solenoid valve 314. The frequency modulator 316generates different electrical wave frequencies and forms, which aretranslated into the movement of the solenoid valve 314 by the valvecontroller 318. The wave forms generated from the frequency modulator316 comprise sinusoidal, square, and sawtooth waves. The wave formsgenerated from the frequency modulator 316 typically have frequenciesless than about 500 Hz, in some modes of operation less than about 20 Hzor less than about 5 Hz. The wave forms have duty cycles ranging from0%, in which the solenoid valve 314 is fully shut, to 100%, in which thesolenoid valve 314 is fully open.

Valve controller 318 modulates the solenoid valve 314 on and off. Thevalve controller 318 may be electrically or mechanically connected tothe solenoid valve 314. Any of a variety of controls may be utilized,including electrical controllers, switches, buttons, levers, rotatableknobs, and others which will be apparent to those of skill in the art inview of the disclosure herein. The valve controller 318 may bemechanically controlled by users or may be electrically controlled bythe frequency modulator 316. The frequency modulator 316 and the valvecontroller 318 may be separate components that are electrically ormechanically connected or a merged component.

Remote control 320 enables physicians to control the frequency modulator316 and/or the valve controller 318 for various purposes, such asturning the valve on/off, selecting different wave frequencies, andselecting different wave forms, while manipulating the catheter 10 atthe patient side. Remote control 320 may be in wired or wirelesscommunication with aspirator 300.

By tuning frequency, duty cycle, and wave form, one skilled in the artmay match or approximate the resonating frequency to the naturalfrequency of the catheter. This may further enhance the efficacy ofaspiration. The natural frequency of the catheter is typically less thanabout 260 Hz.

In another embodiment, shown in FIG. 14, the solenoid valve 414 ispositioned in and fluidly connects between the air/fluid reservoir 422at the atmospheric pressure and the aspiration line 424 connecting thecatheter 10 to the vacuum chamber 410/collection canister 412. Unlikethe first embodiment in FIG. 13, this system modulates pressure in thecatheter 10 by allowing pressure to vary from vacuum to atmosphericpressure. When the solenoid valve 414 is open to the air/fluid reservoir422 at the atmospheric pressure, the vacuum pressure in the aspirationline 424 decreases to the atmospheric pressure. When the solenoid valve414 is closed, it increases the vacuum pressure in the aspiration line424.

In yet another embodiment, shown in FIG. 15, an electro-magneticactuated diaphragm 522 is attached to the aspiration line 524 connectingthe catheter 10 to the vacuum chamber 510/collection canister 512. Theelectromagnetic actuated diaphragm 522, which is similar to that of aspeaker driver, generates acoustic pressure waves in the catheter 10.The diaphragm 522 typically has a structure similar to a speaker driverand comprises frame 526, cone 528, dust cap 530, surround 532, spider ordamper 534, voice coil 536 and magnet 538. Strength of the acousticpressure waves may be modulated by the strength of the magnet 538. Thefrequency modulator 516 connected to the remote control 520 iselectrically connected to the diaphragm 522 and generates differentelectrical wave frequencies and forms, which are translated by thediaphragm 522 into acoustic pressure waves in the aspiration line 524and the catheter 10.

Tortuous vasculature is a common reason for failure to treat vasculatureocclusions in the body due to inability to track the catheter to thelocation of the disease. Navigating catheters through tortuous anatomysuch as neurovasculature can be a challenge. The catheter has to be verysoft as not to damage the vessel wall. At the same time, it also has tobe able to negotiate multiple tight turns without kinking. In addition,it has to have sufficient column strength to transmit force axially foradvancing through the vasculature. All these performance characteristicsare competing design requirements. It is difficult to optimize oneperformance characteristic without sacrificing the others.

Reducing friction between the inner diameter of the vessel and the outerdiameter of the catheter can minimize axial force required to advancecatheter through tortuous vasculature. Therefore, the column strength ofthe catheter may be traded off for optimizing other performancerequirements of the catheter. An example of a method to reduce frictionbetween the inner diameter of the blood vessel and the outer diameter ofthe catheter is to apply a thin layer of coating, usually hydrophilic innature, to the outer diameter of the catheter to reduce its surfacefriction coefficient while in vivo.

In addition or as an alternative to the water hammer constructiondiscussed above, axial mechanical vibration or shock waves may bepropagated to or generated at the distal end of the catheter using avariety of vibration generators, such as spark gap generators,piezoelectric pulse generators, electric solenoids, rotational shaft(wire) having one or more bends or carrying an eccentric weight, or anyof a variety of other impulse generating sources well understood forexample in the lithotripsy arts. Mechanical shock wave or pulsegenerators may be built into the proximal manifold 18, and ormechanically coupled to the manifold or proximal catheter shaft asdesired. Preferably, controls are provided on the manifold or on aproximal control coupled to the manifold, to enable the clinician tovary the intensity and time parameters of the mechanical pulses. Shockwaves may be propagated along the proximal section 33 to assist intranslumenal advance, and/or distal section 34 by way of pull wire 42,depending upon the desired clinical performance.

In an embodiment shown in FIGS. 16 and 17, the distal end 608 of avibrating device 600 is placed in fluid connection with the proximal end12 of the catheter 10 (not illustrated) and generates transverse and/orlongitudinal vibration in the catheter 10. By inducing transversevibration in the catheter 10, it reduces effective contact surface areabetween the vessel and the catheter 10, which in turn reduces surfacefriction force between the inner diameter of the vessel and the outerdiameter of the catheter. In addition, by inducing longitudinalvibration in the catheter 10, the vibrating device 600 breaks staticfriction between the inner diameter of the vessel and the outer diameterof the catheter 10, which reduces overall surface friction. By reducingthe friction between the inner diameter of the vessel and the outerdiameter of the catheter 10, the vibrating device 600 improves cathetertrackability through tortuous vasculatures.

In the illustrated embodiment, the proximal end 602 of the vibratingdevice 600 may be connected to a vacuum pressure source such as a vacuumgenerator. The proximal connector 604 is attached to the housing 606. Inat least one embodiment, the proximal connector 604 may be a luerconnector. The distal end 608 of the vibrating device 600 is connectedto the catheter 10. The distal connector 610 is held in place by aflexible seal 612 that is attached to the housing 606. In at least oneembodiment, the distal connector 610 may be a luer connector. Theflexible seal 612 allows the distal connector 610 to move longitudinallyas well as transversely. The flexible tubing links the proximalconnector 604 and the distal connector 610, creating an aspirationchannel 614 for the fluid to travel through.

The vibrating device has a controller 616 to turn on/off the vibratingaction as well as to vary its frequency. In this embodiment, thecontroller 616 is drawn as a sliding switch. Any of a variety ofcontrols may be utilized, including electrical controllers, switches,buttons, levers, rotatable knobs, and others which will be apparent tothose of skill in the art in view of the disclosure herein.

A vibration generator such as a motor 618 has an eccentrically mountedinertial weight on its shaft generating vibration. Any of a variety ofmotors may be used, including an electric motor, an electro-magneticactuator, and a piezoelectric transducer. The frequency of the vibrationis related to the RPM of the motor 618. A driving circuit 620 isconnected to the motor 618 and the controller 616 and drives the motor618 at different RPMs based on the manipulation of the controller 616.In the illustrated embodiment, the circuit 620 drives the motor 618 atdifferent RPMs based on the position of the sliding switch. A battery622 is connected to and powers the driving circuit 620 and the motor618.

The motor 618 may be mounted perpendicularly to the length of theaspiration channel 614 to create longitudinal vibration. Also, amechanical cam may be attached to the motor 618 to create largermagnitude longitudinal reciprocating motion. The frequency rangegenerated by the electric motor is typically less than about 85 Hz. Toachieve sonic frequencies in the range from about 85 Hz to about 260 Hz,one might replace the electric motor with an electro-magnetic actuator.To achieve ultrasonic frequencies in the range of about 20 Hz to about1.6 MHz, one might employ a piezoelectric transducer.

In yet another embodiment, shown in FIG. 18, an agitator such as stylet702 is permanently or removably inserted into a lumen 40 of the catheter10 and rotated to generate vibration in the catheter 10 and thus improvecatheter trackability through tortuous vasculatures. The stylet 702,whose outer diameter is within the range of from about 0.005 inches(about 0.127 mm) to about 0.035 inches (about 0.889 mm), may have atleast one bend or at least one weight. The peak to peak transversedistance between the bends will be less than the inner diameter of thecatheter 10 when positioned within the catheter. The bends or weights ofthe stylet 702 may be positioned at different locations along the entirelength of the catheter 10 or contained within a vibration zone withinthe distal most 50% or 30% or 10% of the length of the catheterdepending upon desired performance, with the purpose to create the mostdesirable vibration when tracking the catheter 10 through the distalvasculature.

Alternatively, the stylet 702 may have an asymmetric weight such as abead at a distal vibration zone or at its distal end. The stylet 702 maycomprise a monofilament or braided or woven filaments or wires.

In another alternative, the stylet 702 may have a heater (e.g., anelectric coil) at its distal end that facilitates the dissolution of thethrombus or changes the size of the thrombus that is aspirated into thecatheter.

The proximal end of the stylet is attached to a motor driver 704 capableof generating rotational and or axially reciprocating motion at variousfrequencies to form a motor driver-stylet assembly 700. The assembly 700has a controller 706 to turn on/off the rotating action as well as tovary its frequency. In this embodiment, the controller 706 is drawn asan on/off button. Any of a variety of controls may be utilized,including electrical controllers, switches, buttons, levers, rotatableknobs, and others which will be apparent to those of skill in the art inview of the disclosure herein. The proximal luer 708 or other connectorof the catheter 10 reversibly attaches the catheter 10 to the motordriver 804.

Once the catheter 10 has reached its intended location, the entire motordriver-stylet assembly 700 may be detached and removed from the catheter10 leaving a central aspiration lumen.

In patients with vertebral artery occlusions, treatment with angioplastycan result in complications due to embolization of the occlusive lesiondownstream to the basilar artery. Emboli small enough to pass throughthe vertebral arteries into the larger basilar artery are usuallyarrested at the top of the basilar artery, where it bifurcates into theposterior cerebral arteries. The resulting reduction in blood flow tothe ascending reticular formation of the midbrain and thalamus producesimmediate loss of consciousness. The devices described herein can beused to remove thromboembolic material from the vertebral artery or moredistally such as in M1, M2, or M3 arteries.

Agitators for providing vibratory assistance for navigation and/orassisting in the capture and aspiration of debris are described furtherin connection with FIGS. 19-24. Referring to FIG. 19, an agitator 1900may comprise an elongate, flexible body such as a wire or hypo tubehaving a proximal, control end and a distal, active zone or end. Thehypo tube agitator has an inside lumen extending longitudinally thatallows infusion of media. Referring to FIG. 19, an agitator 1900comprises a wire or hypo tube 1904, introduced into the proximal end ofa catheter 1902 and advanced to the distal end 1907 of the catheter1902. The distal tip 1905 of the agitator 1900 may be placed at, beyond,or inside the distal end of the catheter 1902. The agitator 1900 can beeither preloaded into the catheter 1902 and inserted into the patient'sbody together with the catheter 1902 or added after the catheter 1902has been placed. When loaded inside the catheter 1902, the agitator 1900may extend substantially longitudinally along the length of the catheter1902. The agitator 1900 may further comprise a controller at theproximal end to axially adjust the distal tip position. The controllerof the agitator 1900 may be used to axially adjust the position of thedistal tip 1905 when the agitator 1900 is introduced into a variablelength catheter such as that discussed in connection with FIG. 3.

In one implementation of the invention, the agitator and drive systemare configured as a stand-alone device. Once the distal section 34 (FIG.3B) has been positioned within a few (e.g., no more than about 3 or 2)centimeters of the obstruction, the distal end of agitator 1900 maybeintroduced into the proximal end of central lumen 45 of pull wire 42.Agitator 1900 may thereafter be distally advanced so that a distalsegment of agitator 1900 extends beyond the distal end of pull wire 42,and into the distal section 34. The portion of the agitator 1900contained within lumen 45 of pull wire 42 is restrained from anysignificant lateral motion. However, the distal portion of agitator 1900which extends beyond the distal end of pull wire 42 is relativelylaterally unconstrained and is able to agitate thrombus to facilitatedrawing the thrombus into and through the distal section 34. Once thethrombus has been drawn proximally under vacuum and with activation ofthe agitator as needed, to reach the step up in ID at the proximal endof distal section 34, the risk of clogging is greatly reduced.

The agitator 1900 may be rotated manually or via a motor 1906 drivenfrom the catheter 1902's proximal end to rotate or translate the distalend of the agitator 1900. The driver 1906 may be connected to theproximal end of the agitator 1900 either permanently or removably. Thedriver 1906 may be a manual driver that is manually controlled such as aguidewire torquer. The driver 1906 may be a motorized driver. Themotorized driver may be manually controlled with respect to one or morefactors such as rotational direction (CCW/CW), speed, duration, etc. Themotorized driver may be automatically controlled with respect to one ormore factors such as direction (CCW/CW), speed, duration, etc. In onemode, the rotational direction of the agitator is periodically reversed.

The automatically controlled driver may comprise an actuator, andactuating the actuator may execute a pre-programmed series of steps. Theactuator may be a button, a dial, a knob, a switch, a lever, a valve, aslide, a keypad, or any combinations thereof. The driver 1906 may alsobe under synchronized control, in which the driver 1906 drives theagitator 1900 in synchronization with aspiration and media injection.The agitator 1900 may be configured to promote motion at the distal endto help engage and move the clot.

Media may be infused into/around the clot area to help liberate the clotfrom the vasculature.

The agitator 1900 comprises a distal end 1912, a proximal end 1914 and adistal tip 1905. The proximal end 1914 of the agitator 1900 has across-section and/or wall thickness that is large enough to transmit thetorque required to rotate the distal end 1912 of the agitator 1900 whenplaced in the catheter 1902, within the curved vasculature. The outerdiameter of the agitator 1900 may be from about 0.25 mm to about 0.65mm, from about 0.3 mm to about 0.6 mm, from about 0.35 mm to about 0.55mm, from about 0.4 mm to about 0.5 mm, from about 0.42 mm to about 0.48mm, or from about 0.44 mm to about 0.46 mm. In case of the hypo tube1904, the wall thickness of the hypo tube 1904 may be from about 0.01 mmto about 0.29 mm, from about 0.05 mm to about 0.25 mm, from about 0.1 mmto about 0.2 mm, from about 0.12 mm to about 0.18 mm, from about 0.13 mmto about 0.17 mm, or from about 0.14 mm to about 0.16 mm.

The agitator 1900 may additionally be provided with a guide tube 1910,such as a hypo tube, to allow the agitator to spin, or axially orrotationally reciprocate, while constraining a proximal drive segment ofthe agitator 1900 against lateral motion. A distal end 1911 of guidetube 1910 may be positioned within about 25 cm or within about 20 cm or15 cm or less of the distal end of the agitator 1900, depending upondesired performance. The distal section of the agitator 1900, extendingbeyond distal end 1911 of guide tube 1910, is laterally unconstrainedwithin the ID of distal segment 34 and available to agitate andfacilitate aspiration of material into and through the central lumen.

The diameter of the agitator 1900 may be constant along its longitudinallength. The diameter of the agitator 1900 may increase or decrease alongits longitudinal length to coincide with features of the catheter 1902.In one implementation, the diameter of the agitator 1900 decreases inthe distal direction along its longitudinal length by at least one stepor tapered zone to provide increasing flexibility.

The distal end 1912 of the agitator 1900 may be straight. Alternatively,the distal end 1912 of the agitator 1900 may be curved or formed intodifferent shapes to interact with the clot. FIG. 19 illustrates a bend1917 spaced apart from the distal tip 1905 by a motion segment 1909having a length of from about 1 mm to about 15 mm. FIGS. 20A-20C depictmore complex exemplary shapes of the motion segment 1909 of the agitator1900. FIGS. 20D-20E depict an agitator positioned within a swellablepolymer distal funnel tip.

The agitator 1900 may be comprise a single, uniform material or multiplematerials. The materials of the agitator 1900 may be processed (e.g.,heat treatment/annealing) to give varying properties for the localperformance requirements. The agitator 1900 may be structured to provideflexibility while exhibiting high torque transmission. The agitator 1900may made of Nitinol, 304 Stainless Steel, 316 LVM Stainless Steel, PTFE,Parylene, or any combinations thereof. At least a portion of the surfaceof the agitator 1900 may be coated. The entire length of the agitator1900 may be coated. The coating on the agitator 1900 may providelubrication between the ID wall of the catheter 1902 and the agitator1900. In a case that an intermediate hypotube is placed between the wallof the catheter 1902 and the agitator 1900, e.g., constraining tube 1910or tubular pull wire 42, the coating on the agitator 1900 may providelubrication between the intermediate hypotube and the proximal driveportion of the agitator 1900. The coating materials of the wire or hypotube 1904 include PTFE, Parylene, Teflon, or any combinations thereof.

Any of the ID or OD of any of the catheter shafts or other cathetercomponents disclosed herein may be provided with a lubricious coating ormay be made from a lubricious material. For example, a hydrophilicpolymer such as Polyacrylamide, PEO, thermoplastic starch, PVP,copolymers of hydrophilic polymer can be extruded with hydrophobicpolymers such as PEO soft segmented polyurethane blended with Tecoflex.The lubricious coating or the lubricious material may include surfacemodifying additive (SMA) during melt processing. The lubricious coatingor the lubricious material contributes to at least ease of navigation,lower ID skin friction, or better clot removal. In some embodiments,post processing wire ebeam, Gamma, UV, etc. additionally may bedesirable to expose to moisture, temperature, etc. Catheters may be madefrom PEO impregnated polyurethanes such as Hydrothane, Tecophilicpolyurethane for both OD and ID lubricity and inherent thromboresistantproperty without requiring a secondary coating process.

Referring to FIG. 20A, the distal end 2012 of the agitator 1900 maycomprise a coil 2020 to grip a corked clot and wiggle the distal end2010 of the catheter 2002 and the clot during rotation 2006. The coil2020 may be a tight, offset coil, and may comprise at least one andoptionally two or three or more complete revolutions.

Referring to FIG. 20B, the distal end 2012 of the agitator 1900 maycomprise a hook 2022 to grip and emulsify a clot. The hook 2022 may beconcave proximally, or may extend transversely to the axis of theagitator body, extending in a circumferential orientation. Referring toFIG. 20C, the distal end 2012 of the agitator 1900 may comprise a loosecoil or spring 2024. The loose coil or spring 2024 may expand (lengthen)and contract (shorten) with a change in direction of rotation.

Referring to FIGS. 20D-20E, the distal end 2012 of the agitator 2000 maycomprise a coil 2026 to grip a corked clot and wiggle the distal end2010 of the catheter 2002 and the clot during rotation. In addition, thedistal end 2010 of the catheter 2002 may include a polymer sidewall thatreforms by hydration. The coil 2026 maintains a guide wire lumen duringplacement of the catheter. The polymer enables the distal end 2010 ofthe catheter 2002 to expand to a funnel shape after absorption of serumfrom blood. See FIG. 20E.

Referring to FIGS. 21A-21B, the distal tip 2110 of the catheter 2102 maymove or wiggle by interacting with the agitator 1900. When the distalend of the agitator 1900 rotates (e.g., via a driver 2106), the motionsegment 1909 and distal tip 1905 of the agitator interact with the sidewall of the catheter 2102 which wiggles as shown by broken lines 2112.The length of the motion segment, stiffness of the agitator 1900 androtational velocity determines the interaction with the wall of thecatheter 2102 and the amount of wiggle transmitted to the catheter 2101with rotation of the agitator 1900.

Alternatively, the distal tip 2110 of the catheter 2102 may move orwiggle by pulsed media jets existing one or more holes near the distalend of the hypo tube 2124. The hypo tube 2124 has an inside lumenextending along the longitudinal length of the hypo tube 2124. One ormore side holes 2128 may be placed near the distal end of the hypo tube2124 and allow fluid communication between the lumen of the hypo tube2124 and the outside of the hypo tube 2124 (i.e., the lumen of thecatheter 2102). Media (e.g. saline) may be introduced under pressureinto the proximal end of the hypo tube 2124, through the lumen of thehypo tube 2124, and then through the one or more holes of the hypo tube2124. When media is injected into the hypo tube 2124 in a pulsed manner,pulsed media jets eject from the holes of the hypo tube 2124 andtransmit forces on the wall of the catheter 2102, resulting in a wigglemotion of the catheter 2102. The hypo tube 2124 may additionally rotate(e.g., via a driver 2106) to facilitate a wiggle motion of the catheter2102.

Referring to FIGS. 22A-22B, the hypo tube 2204 may have one or moreholes 2210 and is bent near its distal portion to provide a motionsegment 1909. Media (e.g. saline, a drug, a lubricant such aspolyethylene glycol) is injected from the proximal end 2200, through theinside lumen, and out of the holes 2210 of the hypo tube 2204 (directionof media ejection shown as 2208). Vacuum is applied to the central lumenat the proximal end 2200 of the catheter 2202 such that media ejectingfrom the holes 2210 of the hypo tube 2204 is drawn proximally along thecentral lumen of the catheter 2202 toward its proximal end 2200.

As the hypo tube 2204 rotates, the hypo tube 2204 ejects media andsimultaneously makes the distal tip of the catheter 2202 wriggle. Whenthe distal tip of the catheter 2202 wriggles by the rotation of the hypotube 2204, the wriggle of the catheter 2202 may push the clot 2214 fromside to side, and the hypo tube 2204 simultaneously ejects media at theinterface between the clot 2214 and the catheter 2202, providing alubricious avenue for the clot 2214 to release and flow into thecatheter 2202.

With or without injection of media, rotation of the motion segment 1909helps to break up or reshape the thrombus and facilitate entry into theaspiration lumen. In certain situations, the clot can be aspiratedcompletely within the central lumen. In other situations, the clot mayonly be able to be partially drawn into the central lumen, such asillustrated in FIG. 22B. In this situation, rotation of the agitator maybe stopped with application of vacuum remaining on to retain the clot onthe distal end of the catheter. The catheter may then be proximallywithdrawn, pulling the clot along with it, into the access sheath andout of the proximal vascular access point.

Referring to FIGS. 23A-23B, the hypo tube 2304 may have one or moreholes along its surface more proximal from the distal end to facilitatethe movement or flow of the clot 2314 inside the catheter 2302 towardits proximal end 2300. Vacuum 2316 is applied at the proximal end 2300of the catheter 2302 to move the removed clot 2314 from the distal endto the proximal end 2300 of the catheter 2302. As shown in FIG. 23A, theholes may provide a thin film 2312 around the inside of the wall of thecatheter 2302 to facilitate the flow of media and/or the clot 2314 andminimize any clogging of the clot 2314. As shown in FIG. 23B, the hypotube 2304 may have one or more holes to provide media jets ejectingradially from the hypo tube 2304 to grab, pull, and/or emulsify the clot2314 as the clot 2314 passes by the one or more holes on the surface ofthe hypo tube 2304.

Referring to FIG. 24, a vacuum port 2416 may be provided near theproximal end 2400 of the catheter 2402 such as on the manifold forreleasable connection to a vacuum source to aspirate the clot from thevasculature. This allows the vacuum port 2416 to be distinct from theproximal port 2417 for receiving the agitator 1900. This can minimizethe risk that the movement or control of the wire or hypo tube 2404 atits proximal end may be adversely affected by vacuum, aspirated clot,and/or media. The vacuum port may be connected to the catheter 2400 viaa rotating hemostasis valve, discussed below.

Referring to FIGS. 25A-25C, experiments showed that an interruptedvacuum can help aspirating a corked clot stuck at the distal end 2512 ofthe catheter 2510 by loosening the clot and reshaping it to fit into thecatheter 2510 after each vacuum and release cycle. Merely stopping thevacuum is not sufficient to loosen the clot. Completely releasing(venting to atmospheric pressure) the vacuum and allowing the clot torelax before reapplying a vacuum is found to aspirate the corked clotmost efficiently. The period of each vacuum and release cycle may beequal to or greater than about 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, or10 seconds.

FIGS. 25A-25C show a logical progression of the vacuum and release cycleas applied to the catheter 2510. A release line 2518 and a vacuum line2520 are connected to or near the proximal end of the catheter 2510. Therelease line 2518 is in communication with atmospheric pressure on itsproximal end and has a release valve 2514 configured to open or closethe fluid communication between the catheter 2510 and the vacuum. Thevacuum line 2520 is connected to vacuum on its proximal end and has avacuum valve 2516 configured to open or close the fluid communicationbetween the catheter 2510 and the vacuum.

In the first step as shown in FIG. 25A, the release valve 2514 isclosed, and the vacuum valve 2516 is open such that the vacuum isapplied to the catheter 2510 to aspirate the clot. Then, as shown inFIG. 25B, the release valve 2514 is opened while the vacuum valve 2516stays open. Because the release line 2518 and the vacuum line 2520 arein fluid communication, either directly or via at least a portion of thecatheter 2510, the vacuum is applied mainly through the release line2518, dropping vacuum applied to the catheter. Finally, as shown in FIG.25C, the vacuum valve 2516 is shut off, allowing the vacuum to becompletely released and the clot to relax. Then, another cycle from FIG.25A to FIG. 25C begins by closing the release valve 2514 and opening thevacuum valve 2516.

Referring to FIG. 26, there is illustrated a proximal drive assemblyand/or the rotating hemostasis valve to provide the interface fordriving the agitator 1900, providing the port for injecting media, andthe aspiration port. Referring to FIGS. 26, 27A, 27B, and 28, theproximal drive assembly 2602 and the rotating hemostasis valve 2620 maybe releasably or permanently coupled to the proximal end of the agitator1900. The proximal portion of the agitator 1900 passes proximallythrough a lumen of the rotating hemostasis valve 2620 and then that ofthe proximal drive assembly 2602. The proximal end of the agitator 1900may terminate inside the lumen of the proximal drive assembly 2602. Thedistal portion of the proximal drive assembly 2602 is inserted into theproximal end of the rotating hemostasis valve 2620. In anotherembodiment, the proximal drive assembly 2602 may be integrated into therotating hemostasis valve 2620.

The rotating hemostasis valve (RHV) 2620 comprises a distal connector2630 at its distal end, which is configured to couple the rotatinghemostasis valve to the proximal end of the catheter (not shown). Thedistal connector 2630 may be a luer connector. The rotating hemostasisvalve 2620 comprises a central lumen along its longitudinal length,through which a proximal section of agitator 1900 passes. The rotatinghemostasis valve 2620 further comprises an aspiration port 2622, whichbifurcates from the central lumen of the rotating hemostasis valve 2620and provides the aspiration flow path. The rotating hemostasis valve2620 comprises a RHV seal 2626 and a proximal rotating collar 2628 atits proximal end. The proximal rotating collar 2628 controls the openingand closing of the RHV seal 2626. The user (e.g., physician) can eitheropen or close the RHV seal 2626 by rotating the proximal rotating collar2628. The RHV seal 2626, when closed, does not allow fluid communicationbetween the inside lumen distal of the RHV seal 262 and the inside lumenproximal of the RHV seal 262. At the same time, the RHV seal 262 doesnot hamper the longitudinal movement of the distal portion of theproximal drive assembly 2602 inside the rotating hemostasis valve 2629.

Experiments showed that as the wire or hypo tube 1900 is rotated backand forth (i.e., oscillating), the distal end of the agitator 1900changes its position relative to the catheter. The distal end of theagitator 1900 was shown to foreshorten/lengthen as the wire or hypo tube2624 wound/unwound within the catheter due to the rotation of theagitator 1900 or the increase/decrease in media injection pressure. Theproximal rotating collar 2628 and the RHV seal 2626 permit the user(e.g., physician) to account for this variance in length andadvance/withdraw the agitator 1900 relative to the catheter and fix itin place by simply moving the proximal drive assembly 2602 in/out of therotating hemostasis valve 2629. If the agitator 1900 is preloaded intothe catheter, the distance may be initially set at a nominal position.In another embodiment, the proximal rotating collar 2628 of the rotatinghemostasis valve 2620 may be part of the proximal drive assembly 2602.

The proximal drive assembly 2602 comprises a proximal drive connector2604, to which the driver is connected, and a media injection port 2610,into which media is injected. The proximal drive assembly also comprisesa bearing 2606, which allows free rotation of the proximal driveconnector 2604 with respect to the proximal drive assembly 2602. Theproximal drive connection 2604 may be coupled to the proximal end of theagitator 1900 such that the rotation of the proximal drive connector2604 is translated to the rotation of the wire or hypo tube 1900. Theproximal drive assembly further comprises a drive tube seal 2608, whichprevents fluid communication between the inside lumen (of the proximaldrive assembly 2602) distal of the drive tube seal 2608 and the insidelumen proximal of the drive tube seal 2608.

Referring to FIG. 29, the driver 2950 is removably connected to theproximal end of the proximal drive assembly 2902 via the proximal driveconnection 2604. The driver 2950 is configured to drive the agitator1900. The driver 2950 is a motorized driver that is automaticallycontrolled with respect to one or more factors such as direction(CCW/CW), speed, duration, etc. The driver 2950 comprises a control 2954such as a button, which executes a pre-programmed series of steps whenpushed. The driver 2954 may be under synchronized control, in which thedriver 2954 drives the agitator 1900 in synchronization with aspirationand media injection, when the back of the driver 2950 is plugged intothe synchronization port 2952.

The system for retrieving clots comprises the aspiration catheter; theagitator 1900 longitudinally extendable inside the lumen of theaspiration catheter; and the driver connectable to the proximal end ofthe agitator 1900 (e.g., via the rotating hemostasis valve or theproximal drive assembly) with or without a synchronization port. Thesystem may allow impulse aspiration and/or impulse injection of media.The media may comprise water, saline solution, or media with aneffective amount of drug (e.g., drug therapy such as heparin, plavix,tPA). The components may be manipulated individually or in asynchronized manner using predetermined operating parameters (e.g., forsynchronized aspiration, injection, and rotation).

The method of retrieving a clot may comprise providing the aspirationcatheter, the agitator longitudinally extending or positionable insidethe lumen of the aspiration catheter; and the driver coupled to theproximal end of the agitator; placing the catheter adjacent to the clot;attempting to aspirate clot; if not successful, advancing an agitatordistally through the catheter; activating the driver to rotate theagitator and loosen the clot; optionally injecting media through theagitator to lubricate the clot and/or create a media jet from the distalend of the agitator, configured to help aspirate the clot; transportingthe clot proximally inside the lumen of the catheter by applying thevacuum at the proximal end of the catheter; and optionally pulsing thevacuum. As pieces of the clot separate, transport may be assisted by therotating agitator and/or injection media.

In order to detach a more stubborn clot, aspiration, media injection,and/or rotation of the wire or hypo tube may be timed. Building up asurplus of media around the clot will form a plug. When aspiration isactivated and/or pulsed, the vacuum can draw the “plug” proximallyinside the lumen of the wire or hypo tube like a syringe plunger. Ahigher local vacuum around the clot is maintained, and more momentum isadded to the “plug” as more media is added. Timing the rotation of thewire or hypo tube with aspiration and media injection may help wiggle orfatigue the clot and detach it out of the vasculature.

Any of the catheter shaft or sections of the catheter shaft ortelescoping extensions in accordance with the present invention maycomprise a multi-layer construct having a high degree of flexibility andsufficient push ability to reach deep into the cerebral vasculature,such as at least as deep as the petrous, cavernous, or cerebral segmentof the internal carotid artery (ICA).

In one example, referring to FIG. 30, the catheter 3000 may have aneffective length from the manifold to distal tip from about 70 cm toabout 150 cm, from about 80 cm to about 140 cm, from about 90 cm toabout 130 cm, from about 100 cm to about 120 cm, or from about 105 cm toabout 115 cm. The outer diameter of the catheter 3000 may be from about0.07 inches to about 0.15 inches, from about 0.08 inches to about 0.14inches, from about 0.09 inches to about 0.13 inches, from about 0.1inches to about 0.12 inches, or from about 0.105 inches to about 0.115inches, and may be lower in a distal segment than in a proximal segment.The inner diameter 3108 of the catheter 3000 in a single central lumenembodiment may be greater than or equal to about 0.11 inches, greaterthan or equal to about 0.1 inches, greater than or equal to about 0.09inches, greater than or equal to about 0.088 inches, greater than orequal to about 0.08 inches, greater than or equal to about 0.07 inches,greater than or equal to about 0.06 inches, or greater than or equal toabout 0.05 inches. The inner diameter 3108 of the catheter 3000 in asingle central lumen embodiment may be less than or equal to about 0.11inches, less than or equal to about 0.1 inches, less than or equal toabout 0.09 inches, less than or equal to about 0.088 inches, less thanor equal to about 0.08 inches, less than or equal to about 0.07 inches,less than or equal to about 0.06 inches, or less than or equal to about0.05 inches. Referring to FIG. 30, an inner liner 3014 may be formed bydip coating a mandrel (not shown) to provide a thin walled tubularinside layer of the catheter body 3000. The dip coating may be producedby coating a wire such as a silver coated copper wire in PTFE. Themandrel may thereafter be axially elongated to reduce diameter, andremoved to leave the tubular inner liner. The outside surface of thetubular inner liner 3014 may thereafter be coated with a soft tie layer3012 such as polyurethane (e.g., Tecoflex™), to produce a layer having athickness of no more than about 0.005 inches, and in someimplementations approximately 0.001 inches. The tie layer 3012 willgenerally extend along at least about the most distal 10 cm or 20 cm ofthe catheter shaft 3000 generally less than about 50 cm and may in oneimplementation extend approximately the distal 30 cm of the cathetershaft 3000, 3100.

A braid such as a 75 ppi stainless steel braid 3010 may thereafter bewrapped around the inner liner 3014 through a proximal zone up to adistal transition 3011. From the distal transition 3011 to the distalend of the catheter 3000, a coil 3024 comprising a shape memory materialsuch as a Nitinol alloy may thereafter be wrapped around the inner liner3014. In one implementation, the Nitinol coil has a transitiontemperature below body temperature so that the Nitinol reside in theaustinsite (springy) state at body temperature. Adjacent loops or filarsof the coil may be closely tightly wound in a proximal zone with adistal section having looser spacing between adjacent loops. In anembodiment having a coil section 3024 with an axial length of betweenabout 20% and 30% of the overall catheter length, (e.g., 28 cm coillength in a 110 cm catheter shaft 3000), at least the distal 1 or 2 or 3or 4 cm of the coil will have a spacing that is at least about 130%, andin some implementations at least about 150% or more than the spacing inthe proximal coil section. In a 110 cm catheter shaft 3000 having aNitinol coil the spacing in the proximal coil may be about 0.004 inchesand in the distal section may be at least about 0.006 inches or 0.007inches or more.

The distal end of the coil 3024 is spaced proximally from the distal endof the inner liner 3014 to provide room for an annular radiopaque marker3040. In one embodiment, the distal end of the catheter 3000 is providedwith a beveled distal surface 3006 residing on a plane having an angleof at least about 10° or 20° and in one embodiment about 30° withrespect to a longitudinal axis of the catheter 3000. The radiopaquemarker 3040 may reside in a plane that is transverse to the longitudinalaxis. Alternatively, at least the distally facing edge of the annularradiopaque marker 3040 may be an ellipse, residing on a plane which isinclined with respect to the longitudinal axis to complement the bevelangle of the distal surface 3006.

After applying the proximal braid 3010, the distal coil 3024 and the ROmarker 3040 an outer Jacket 3020 maybe applied such as a shrink wraptube to enclose the catheter body 3000. The outer shrink-wrapped sleeve3020 may comprise any of a variety of materials, such as polyethylene,polyurethane, PEBAX, nylon or others known in the art. Sufficient heatis applied to cause the polymer to flow into and embed the proximalbraid and distal coil.

In one implementation, the outer shrink wrap jacket 3020 is formed bysequentially advancing a plurality of short tubular segments 3022, 3026,3028, 3030, 3032, 3034, 3036, 3038 concentrically over the cathetershaft subassembly, and applying heat to shrink the sections on to thecatheter 3000 and provide a smooth continuous outer tubular body. Theforegoing construction may extend a long at least the most distal 10 cm,and preferably at least about the most distal 20 or 25 cm of thecatheter body 3000.

The durometer of the outer wall segments may decrease in a distaldirection. For example, proximal segments such as 3022 and 3026, mayhave a durometer of at least about 60 or 70 D, with gradual decrease indurometer of successive segments in a distal direction to a durometer ofno more than about 35 D or 25 D or lower. A 25 cm section may have atleast about 3 or 5 or 7 or more segments and the catheter 3000 overallmay have at least about 6 or 8 or 10 or more distinct flexibility zones.The distal 1 or 2 or 4 or more segments 3036, 3038, may have a smallerOD following shrinking than the more proximal segments 3022-3034 toproduce a step down in OD for the finished catheter body 3000. Thelength of the lower OD section 3004 may be within the range of fromabout 3 cm to about 15 cm and in some embodiments is within the range offrom about 5 cm to about 10 cm such as about 7 or 8 cm, and may beaccomplished by providing the distal segments 3036, 3038 with a lowerwall thickness.

Referring to FIGS. 31A-31C, the catheter may further comprise a tensionsupport for increasing the tension resistance in the distal zone. Thetension support may comprise a filament and, more specifically, maycomprise one or more axially extending filaments 3042. The one or moreaxially extending filaments 3042 may be axially placed inside thecatheter wall near the distal end of the catheter. The one or moreaxially extending filaments 3042 serve as a tension support and resistelongation of the catheter wall under tension (e.g., when the catheteris being proximally retracted through tortuous vasculature). At leastone of the one or more axially extending filaments 3042 may proximallyextend along the length of the catheter wall from near the distal end ofthe catheter to less than about 5 cm from the distal end of thecatheter, less than about 10 cm from the distal end of the catheter,less than about 15 cm from the distal end of the catheter, less thanabout 20 cm from the distal end of the catheter, less than about 25 cmfrom the distal end of the catheter, less than about 30 cm from thedistal end of the catheter, less than about 35 cm from the distal end ofthe catheter, less than about 40 cm from the distal end of the catheter,or less than about 50 cm from the distal end of the catheter. The one ormore axially extending filaments 3042 may have a length greater than orequal to about 50 cm, greater than or equal to about 40 cm, greater thanor equal to about 35 cm, greater than or equal to about 30 cm, greaterthan or equal to about 25 cm, greater than or equal to about 20 cm,greater than or equal to about 15 cm, greater than or equal to about 10cm, or greater than or equal to about 5 cm. At least one of the one ormore axially extending filaments 3042 may have a length less than orequal to about 50 cm, less than or equal to about 40 cm, less than orequal to about 35 cm, less than or equal to about 30 cm, less than orequal to about 25 cm, less than or equal to about 20 cm, less than orequal to about 15 cm, less than or equal to about 10 cm, or less than orequal to about 5 cm. At least one of the one or more axially extendingfilaments 3042 may extend at least about the most distal 50 cm of thelength of the catheter, at least about the most distal 40 cm of thelength of the catheter, at least about the most distal 35 cm of thelength of the catheter, at least about the most distal 30 cm of thelength of the catheter, at least about the most distal 25 cm of thelength of the catheter, at least about the most distal 20 cm of thelength of the catheter, at least about the most distal 15 cm of thelength of the catheter, at least about the most distal 10 cm of thelength of the catheter, or at least about the most distal 5 cm of thelength of the catheter.

The one or more axially extending filaments 3042 may be placed near orradially outside the tie layer 3012 or the inner liner 3014. The one ormore axially extending filaments 3042 may be placed near or radiallyinside the braid 3010 and/or the coil 3024. The one or more axiallyextending filaments 3042 may be carried between the inner liner 3014 andthe helical coil 3024.

When more than one axially extending filaments 3042 are placed in thecatheter wall, the axially extending filaments 3042 may be placed in aradially symmetrical manner. For example, the angle between the twoaxially extending filaments 3042 with respect to the radial center ofthe catheter may be about 180 degree. Alternatively, depending ondesired clinical performances (e.g., flexibility, trackability), theaxially extending filaments 3042 may be placed in a radiallyasymmetrical manner. The angle between any two axially extendingfilaments 3042 with respect to the radial center of the catheter may beless than about 180 degree, less than or equal to about 165 degree, lessthan or equal to about 150 degree, less than or equal to about 135degree, less than or equal to about 120 degree, less than or equal toabout 105 degree, less than or equal to about 90 degree, less than orequal to about 75 degree, less than or equal to about 60 degree, lessthan or equal to about 45 degree, less than or equal to about 30 degree,less than or equal to about 15 degree, less than or equal to about 10degree, or less than or equal to about 5 degree.

The one or more axially extending filaments 3042 may be made ofmaterials such as Kevlar, Polyester, Meta-Para-Aramide, or anycombinations thereof. At least one of the one or more axially extendingfilaments 3042 may comprise a single fiber or a multi-fiber bundle, andthe fiber or bundle may have a round or rectangular cross section. Theterms fiber or filament do not convey composition, and they may compriseany of a variety of high tensile strength polymers, metals or alloysdepending upon design considerations such as the desired tensile failurelimit and wall thickness. The cross-sectional dimension of the one ormore axially extending filaments 3042, as measured in the radialdirection, may be no more than about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%,10%, 11%, 12%, 13%, 14%, 15%, 20%, 25%, or 30% of that of the catheter3000. The cross-sectional dimension of the one or more axially extendingfilaments 3042, as measured in the radial direction, may be no more thanabout 0.001 inches, about 0.002 inches, about 0.003 inches, about 0.004inches, about 0.005 inches, about 0.006 inches, about 0.007 inches,about 0.008 inches, about 0.009 inches, about 0.010 inches, about 0.015inches, about 0.020 inches, about 0.025 inches, or about 0.030 inches.

The one or more axially extending filaments 3042 may increase thetensile strength of the distal zone of the catheter to at least about 1pound, at least about 2 pounds, at least about 3 pounds, at least about4 pounds, at least about 5 pounds, at least about 6 pounds, at leastabout 7 pounds, at least about 8 pounds, or at least about 10 pounds ormore.

Referring to FIGS. 32A-32C, depending on whether the catheter 3000 isable to navigate sufficiently distally to reach the target site, anintraluminal catheter 3200 such as a telescopic extension segment havinga proximally extending control wire as has been described elsewhereherein (e.g., distal segment 34 in FIGS. 3A and 3B) may be insertedthrough the catheter 3000 from the proximal end of the catheter 3000.The intraluminal catheter 3200 is inserted such that the distal end ofthe intraluminal catheter 3200 reaches further distally beyond thedistal end of the catheter 3000. The outer diameter of the intraluminalcatheter 3200 is smaller than the inner diameter of the catheter 3000.This way, the intraluminal catheter 3200 can slide inside the lumen ofthe catheter 3000.

The intraluminal catheter 3200 incorporates characteristics of the sidewall construction of the catheter 3000 described herein. The axiallength of the tubular extension segment may be less than about 50% andtypically less than about 25% of the length of the catheter 3000. Theaxial length of the tubular extension segment will generally be at leastabout 10 cm or 15 cm or 20 cm or 25 cm or more but generally no morethan about 70 cm or 50 cm or 30 cm.

Referring to FIGS. 33A-33C, the intraluminal catheter 3200 may have oneor more axially extending filaments 3242. The one or more axiallyextending filaments 3242 incorporate characteristics of the one or moreaxially extending filaments 3042 of the catheter 3000, except thecross-sectional dimension as measured in the radial direction of the oneor more axially extending filaments 3242 of the intraluminal catheter3200 may be less than the corresponding dimension of the filament 3042in the catheter 3000.

Referring to FIGS. 34A-34B, there is illustrated one example of an outerjacket segment stacking pattern for a progressive flexibility catheterof the type discussed in connection with FIG. 30. A distal segment 3038may have a length within the range of about 1-3 cm, and a durometer ofless than about 35 D or 30 D. An adjacent proximal segment 3036 may havea length within the range of about 4-6 cm, and a durometer of less thanabout 35 D or 30 D. An adjacent proximal segment 3034 may have a lengthwithin the range of about 4-6 cm, and a durometer of about 35 D or less.An adjacent proximal segment 3032 may have a length within the range ofabout 1-3 cm, and a durometer within the range of from about 35 D toabout 45 D (e.g., 40 D). An adjacent proximal segment 3030 may have alength within the range of about 1-3 cm, and a durometer within therange of from about 50 D to about 60 D (e.g., about 55 D). An adjacentproximal segment 3028 may have a length within the range of about 1-3cm, and a durometer within the range of from about 35 D to about 50 D toabout 60 D (e.g., about 55 D). An adjacent proximal segment 3026 mayhave a length within the range of about 1-3 cm, and a durometer of atleast about 60 D and typically less than about 75 D. More proximalsegments may have a durometer of at least about 65 D or 70 D. The distalmost two or three segments may comprise a material such as Tecothane,and more proximal segments may comprise PEBAX or other catheter jacketmaterials known in the art. At least three or five or seven or nine ormore discrete segments may be utilized, having a change in durometerbetween highest and lowest along the length of the catheter shaft of atleast about 10 D, preferably at least about 20 D and in someimplementations at least about 30 D or 40 D or more.

Performance metrics of a catheter include back-up support, trackability,pushability, and kink resistance. Back-up support means ability of thecatheter to remain in position within anatomy and provide a stableplatform through which endoluminal devices may advance. Referring toFIG. 35, when the devices are pushed through the catheter 3202, if thereis not enough back-up support in the catheter 3202, the distal portion3204 of the catheter 3202 may prolapse, pull out, or back out of avessel 3206 that branches out of a main blood vessel (e.g.,brachiocephalic artery 82, common carotid artery 80, or subclavianartery 84). Back-up support for the catheter 3202 may be improved byproviding a proximal region with high durometer or modulus and a distalregion with low durometer or modulus. Durometer or modulus of theproximal region of the catheter 3202 may be improved by braidreinforcement. The region of the catheter at which durometer or modulusis strengthened may be placed near branching points at which the aorticarch 1114, 1214 branches into brachiocephalic artery 82, common carotidartery 80, or subclavian artery 84 or near other anatomical structures(i.e., branching points) at which a main vessel branches into one ormore smaller vessels, providing an opportunity for a catheter with poorback-up support to prolapse. For example, the region of the catheter atwhich durometer or modulus is strengthened may be placed within about0.5 cm, about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm, orabout 6 cm from a branching point at which a main vessel branches intoone or more smaller vessels.

Trackability means ability of the catheter to track further distallythan other catheters (e.g., to M1). For example, a catheter that canreach a cerebral segment of the internal carotid artery (ICA) has bettertrackability than a catheter that can reach a cavernous or petroussegment of the ICA. Trackability of the catheter may be improved byusing a catheter wall with low durometer or modulus or by adding acoating (e.g., a hydrophilic coating) on at least a portion of thecatheter wall. In one embodiment, the hydrophilic coating may be placedalong the distal most region of the catheter. The hydrophilic coating onthe catheter may extend to about 1 cm, about 5 cm, about 10 cm, about 15cm, or about 20 cm from the distal end of the catheter. The region withlower durometer or modulus may locate at the distal most region of thecatheter. The region with lower durometer or modulus may extend to about1 cm, about 5 cm, about 10 cm, about 15 cm, or about 20 cm from thedistal end of the catheter.

Pushability means rigidity of the catheter sufficient to push throughanatomy without “buckling”. Pushability of the catheter may be improvedby increasing its durometer or modulus. Pushability of the catheter mayalso be improved by providing a proximal region with high durometer ormodulus and a distal region with low durometer or modulus. A transitionregion of the catheter in which durometer or modulus changes along itslongitudinal length (e.g., decreasing durometer or modulus from theproximal end to the distal end) may begin at about 50%, 60%, 70%, 75%,80%, or more of the length of the catheter from its proximal end.

Kink resistance means resistance of the catheter to kinking. Inaddition, if the catheter does kink, kink resistance of the catheterhelps it return to its original shape. Kink resistance is important inthe distal segment of the catheter, which is more prone to kinking thanthe proximal segment. Kink resistance of the catheter may be improved byadding one or more NiTi coils (or a coil at least portion of which isNitinol) to the catheter wall.

FIG. 36 describes a graph of durometer or modulus of a catheter inaccordance with the present invention along the length of the catheter,from the proximal end (x=0) to the distal end (x=1). The catheteraccording to an embodiment may have a decreasing durometer or modulus(E) approaching its distal end. The proximal end of the catheter hashigher durometer or modulus than that of the distal end of the catheter.High durometer or modulus near the proximal end provides superiorback-up support of the catheter. Durometer or modulus of the catheter issubstantially constant along its length near the proximal end 3302 ofthe catheter. Then, durometer or modulus of the catheter decreases nearthe distal end 3304 of the catheter. Durometer or modulus of thecatheter may begin to decrease (i.e., transition region) at about 50%,70%, 75%, 80%, or 90% of the length of the catheter from its proximalend. The catheter may have successively decreasing durometer or modulusnear its distal end by using materials with less durometer or modulus orhaving a thinner catheter wall near the distal end. Decreased durometeror modulus near the distal end provides superior trackability of thecatheter.

FIG. 37 describes flexibility test profiles of catheters in accordancewith the present invention compared with conventional catheters.Flexibility of a catheter was measured by the three point flexural testwith a span of one inch and a displacement of 2 mm. In other words, FIG.37 describes a force (i.e., flexural load) necessary to verticallydisplace an one-inch-long catheter segment by 2 mm with respect todistance from strain relief (i.e., proximal end of the catheter) to thepoint of force application. All catheters tested in FIG. 37 show modulusor flexibility profiles similar to one shown in FIG. 36. Modulus of thecatheters stays substantially constant along its length near theproximal end and then gradually decreases near the distal end.

Catheters according to the present invention have a flexural load thatis substantially constant along the longitudinal length near theproximal end and a rapidly decreasing flexural load near the distal end.In a catheter having a length of about 125 cm, the catheters may have aflexural load greater than or equal to about 1.0 lbF, about 1.5 lbF,about 2.0 lbF, about 2.5 lbF, about 3.0 lbF, or about 3.5 lbF at about85 cm from the proximal end. The catheters may have a flexural load lessthan or equal to about 2.5 lbF, about 2.0 lbF, about 1.5 lbF, about 1.0lbF, or about 0.5 lbF at about 95 cm from the proximal end. Thecatheters may have a flexural load less than or equal to about 1.5 lbF,about 1.0 lbF, about 0.75 lbF, about 0.5 lbF, about 0.25 lbF, or about0.1 lbF at about 105 cm from the proximal end. The catheters may have aflexural load less than or equal to about 1.0 lbF, about 0.75 lbF, about0.5 lbF, about 0.4 lbF, about 0.3 lbF, about 0.2 lbF, or about 0.1 lbFat about 115 cm from the proximal end. For catheters having differentlengths, the foregoing dimensions can be scaled from the distal end ofthe catheter as a percentage of catheter length.

In certain implementations constructed in accordance with FIG. 30, theflexural load is less than about 3.0 or 3.25 lbF at 65 cm from theproximal end and greater than about 2.25 or 2.5 lbF on average from 65cm to 85 cm from the proximal end. Flexural load drops to no more thanabout 1.0 and preferably no more than about 0.5 lbF at about 95 cm fromthe proximal end. This provides enhanced backup support in the aortawhile maintaining enhanced trackability into the distal vasculature.

In other embodiments, the catheters may have a flexural load greaterthan or equal to about 1.0 lbF, about 1.5 lbF, about 2.0 lbF, about 2.5lbF, about 3.0 lbF, or about 3.5 lbF at about 60 cm from the proximalend. The catheters may have a flexural load less than or equal to about2.0 lbF, about 1.5 lbF, about 1.0 lbF, or about 0.5 lbF at about 70 cmfrom the proximal end. The catheters may have a flexural load less thanor equal to about 1.0 lbF, about 0.75 lbF, about 0.5 lbF, about 0.4 lbF,about 0.3 lbF, about 0.2 lbF, or about 0.1 lbF at about 80 cm from theproximal end. The catheters may have a flexural load less than or equalto about 1.0 lbF, about 0.75 lbF, about 0.5 lbF, about 0.4 lbF, about0.3 lbF, about 0.2 lbF, or about 0.1 lbF at about 90 cm from theproximal end.

The catheters may have a transition region, in which its flexural loadchanges by greater than or equal to about 1.0 lbF, about 1.5 lbF, about2.0 lbF, about 2.5 lbF, about 3.0 lbF, or about 3.5 lbF. Thelongitudinal length of the transition region may be less than or equalto about 20 cm, about 15 cm, about 10 cm, about 5 cm, about 3 cm, orabout 1 cm.

Compared to Neuron Max (Penumbra, Inc.) 3402, catheters according to thepresent invention (e.g., 3404, 3406, 3408, 3410) have comparable modulusnear its proximal end. This way, the catheters according to the presentinvention provide back-up support comparable to that of Neuron Max. Inaddition, the catheters have modulus that falls more rapidly near thetransition region (between the proximal end and the distal end) thanthat of Neuron Max.

Compared to Ace 68 catheter (Penumbra) 3412, Ace 64 catheter (Penumbra)3414, Benchmark 71 catheter (Penumbra) 3416, and Sofia Plus(MicroVention) 3418, the catheters according to the present inventionshave greater modulus near its proximal end and comparable modulus nearits distal end. This way, the catheters according to the presentinvention provide superior back-up support with comparable trackabilitycompared to conventional catheters. The catheters according to thepresent invention may achieve this modulus profile even when their innerdiameters (and thus lumen volumes) are greater than or equal to those ofAce 68, Ace 64, Benchmark 71, and Sofia Plus, which range from 0.064inch to 0.071 inch.

Referring to FIG. 38, there is illustrated a transformable access sheath200. The access sheath 200 comprises an elongate flexible tubular body202 extending between a proximal end 204 and a distal end 206. Aproximal access port 208 is in communication with a distal port 210 onthe distal end 206 by way of a central lumen 212. See FIG. 39.

At least one transition zone 214 is provided on the tubular body 202.Transition zone 214 is controllably transformable between a relativelystiff configuration and a relatively flexible configuration. The accesssheath 200 may be distally advanced through tortuous anatomy with atleast one transition zone 214 in a relatively stiff configuration asdesired such as to provide column strength or to facilitate theintroduction of instruments therethrough. The transition zone 214 may becontrollably transformed to a relatively flexible configuration asdesired, such as to navigate tight bends in the vasculature.

In the illustrated embodiment, three transition zones 214 are shown.However, one or two or three or four or more transition zones may beutilized, depending upon the desired clinical performance. Thetransition zone 214 may be from about 1 cm to about 20 or 30 cm or morein length. In certain embodiments, the transition zones will be withinthe range of from about 2 cm to about 10 cm in length. The length andlocation of the transition zones may depend upon the target anatomy forthe access catheter, and can be located accordingly.

Referring to FIG. 39, there is illustrated a cross-sectional view takenalong the lines 18-18 of FIG. 38, through a transition zone 214. Thetubular body 202 comprises a sidewall 216 having at least one heatingelement 218 carried by or embedded within the sidewall 216. In theillustrated embodiment, the heater 218 may be an electrically conductivefilament, such as a filar on an electrically conductive helical coil orbraid. The electrically conductive filament may be placed within orlaminated within an inner layer and an outer layer of the sidewall 216.In at least one embodiment, an inner layer of the sidewall 216 maycomprise polytetrafluorothylene (PTFE) for lubricity. In at least oneembodiment, an outer layer of the sidewall 216 may comprisebiocompatible material preferably with a glass transition temperaturefrom about 40° C. to about 80° C.

Alternatively, an electrically conductive polymer may be utilized toform the sidewall 216. Electrically conductive coatings mayalternatively be printed, laminated, embedded or otherwise applied tothe outside, the inside, or laminated within an inner layer and an outerlayer of the sidewall 216. In at least one embodiment, the resistance ofthe heater 218 may be calibrated to a specific heating temperature, suchas 40-80° C., for a predetermined voltage level of the power source.This may eliminate the need for a thermocouple and prevent potentialoverheating.

One or more electrical conductors may extend between the transition zone214 and a proximal activation port 215, adapted for coupling to a sourceof electricity from an external controller. In a mono polarconstruction, a single conductor for each transition zone 214 may extendproximally to the activation port 215. A second conductor may lead to orcomprise an electrically conductive surface on the tubular body 202, forconducting electricity through the body of the patient to an externalelectrode as is understood in the art. Alternatively, in a bipolarembodiment, each transition zone 214 may be provided with at least twoelectrical conductors extending proximally to the activation port 215.

At least the transition zone comprises a biocompatible material that isrelatively firm at body temperature (e.g., 37° C.) but transitions to arelatively soft, flexible material upon application of heat. Typicalsuitable materials have a relatively low melting point so as to besoftenable at temperatures not so high as to damage living vessels. Inany event the material will have a softening point or a glass transitiontemperature above body temperature, with a melting point significantlyabove body temperature and above the temperature reached by activatingthe heating element 218. In one embodiment, the biocompatible materialpreferably has a glass transition temperature from about 40° C. to about80° C. Suitable materials may include polymers with a polymer chainorientation that causes the polymer to break when heated.

Examples of suitable biostable materials are polymers, typicallythermoplastic polymers such as polyolefins and polyurethanes and mostother biocompatible polymers. Typical suitable bioabsorbable materialsinclude polyglycolide (PGA), poly(L-lactide) (PLLA),poly(.epsilon.-caprolactone) (PCL), and blends or combinations thereof.Polyglycolide for example has a glass transition temperature between35-40° C., such having a considerably higher melting point.

Typical operating (softening) temperatures in this regard are on theorder of between about 40 and 80° C., often between about 40° C. and 60°C. to cause a softening transition of the transition zone 214, and allowa transition back to a firm state upon removal of power and reversion ofthe transition zone 214 back to body temperature. A temperature higherthan about 80° C. may be acceptable for a short period of time,depending upon the total energy delivered. Any temperature to which theheater 218 is elevated is limited by what the body of the patient canhandle without causing damage to the vessel wall or causing thrombus toform. For this reason, it may be desirable to remain within the lowerend of the temperature ranges illustrated above if the eligible polymersexhibit suitable flexibility at the softening point temperature andsuitable firmness at the lower body temperature.

Upon being heated, the biocompatible energy-activated transition zone214 softens so that it may be navigated through a tight bend forexample. The material is to be softened enough by the energy applicationso that it increases in flexibility, but retains the structuralintegrity necessary for navigation and retains its shape so that uponinterruption of the heat source it will harden back to its originalconfiguration. To maintain the integrity of the tubular body, side wall216 may be provided with flexible reinforcing structures such as ahelically wrapped wire, ribbon or polymeric strand such as polyimide, orother braid or weave as is understood in the neurovascular catheterarts. A resistance coil or other resistance filaments may also providethe mechanical reinforcing function while the transition zone is in thesoftened state.

Heating may alternatively be provided by positioning a heat source suchas a resistance heat element carried by a heater catheter within thecentral lumen 212. Once the catheter has reached its final position inthe vasculature, the heater catheter may be proximally withdrawn fromthe central lumen 212, which is now available for aspiration or toreceive a distal section 34 therethrough. In either heaterconfiguration, a power source may be provided within or electricallycoupled to a proximal manifold on the aspiration catheter or heatercatheter.

Access for the catheter of the present invention can be achieved usingconventional techniques through an incision on a peripheral artery, suchas right femoral artery, left femoral artery, right radial artery, leftradial artery, right brachial artery, left brachial artery, rightaxillary artery, left axillary artery, right subclavian artery, or leftsubclavian artery. An incision can also be made on right carotid arteryor left carotid artery in emergency situations.

Avoiding a tight fit between the guidewire 40 and inside diameter ofguidewire lumen 28 enhances the slidability of the catheter over theguidewire. In ultra small diameter catheter designs, it may be desirableto coat the outside surface of the guidewire 40 and/or the insidesurface of the wall defining lumen 38 with a lubricous coating tominimize friction as the catheter 10 is axially moved with respect tothe guidewire 40. A variety of coatings may be utilized, such asParalene, Teflon, silicone, polyimide-polytetrafluoroethylene compositematerials or others known in the art and suitable depending upon thematerial of the guidewire or inner tubular wall 38.

Aspiration catheters of the present invention which are adapted forintracranial applications generally have a total length in the range offrom 60 cm to 250 cm, usually from about 135 cm to about 175 cm. Thelength of the proximal segment 33 will typically be from 20 cm to 220cm, more typically from 100 cm to about 120 cm. The length of the distalsegment 34 will typically be in the range from 10 cm to about 60 cm,usually from about 25 cm to about 40 cm.

The catheters of the present invention may be composed of any of avariety of biologically compatible polymeric resins having suitablecharacteristics when formed into the tubular catheter body segments.Exemplary materials include polyvinyl chloride, polyethers, polyamides,polyethylenes, polyurethanes, copolymers thereof, and the like. In oneembodiment, both the proximal body segment 33 and distal body segment 34will comprise a polyvinyl chloride (PVC), with the proximal body segmentbeing formed from a relatively rigid PVC and the distal body segmentbeing formed from a relatively flexible, supple PVC. Optionally, theproximal body segment may be reinforced with a metal or polymeric braidor other conventional reinforcing layer.

The proximal body segment will exhibit sufficient column strength topermit axial positioning of the catheter through a guide catheter withat least a portion of the proximal body segment 33 extending beyond theguide catheter and into the patient's vasculature. The proximal bodysegment may have a shore hardness in the range from 50 D to 100 D, oftenbeing about 70 D to 80 D. Usually, the proximal shaft will have aflexural modulus from 20,000 psi to 1,000,000 psi, preferably from100,000 psi to 600,000 psi. The distal body segment 34 will besufficiently flexible and supple so that it may navigate the patient'smore narrow distal vasculature. In highly flexible embodiments, theshore hardness of the distal body segment 34 may be in the range of fromabout 20 A to about 100 A, and the flexural modulus for the distalsegment 34 may be from about 50 psi to about 15,000 psi.

The catheter body may further comprise other components, such asradiopaque fillers; colorants; reinforcing materials; reinforcementlayers, such as braids or helical reinforcement elements; or the like.In particular, the proximal body segment may be reinforced in order toenhance its column strength and torqueability (torque transmission)while preferably limiting its wall thickness and outside diameter.

Usually, radiopaque markers will be provided at least at the distal end14 and the transition region 32 at the distal end of proximal segment33. One radiopaque marker comprises a metal band which is fully recessedwithin or carried on the outside of the distal end of the proximal bodysegment 33. Suitable marker bands can be produced from a variety ofmaterials, including platinum, gold, and tungsten/rhenium alloy.Preferably, the radiopaque marker band will be recessed in an annularchannel to produce a smooth exterior surface.

The proximal section 33 of tubular body 16 may be produced in accordancewith any of a variety of known techniques for manufacturinginterventional catheter bodies, such as by extrusion of appropriatebiocompatible polymeric materials. Alternatively, at least a proximalportion or all of the length of tubular body 16 may comprise a polymericor metal spring coil, solid walled hypodermic needle tubing, or braidedreinforced wall, as is known in the microcatheter arts.

In a catheter intended for neurovascular applications, the proximalsection 33 of body 16 will typically have an outside diameter within therange of from about 0.117 inches to about 0.078 inches. In oneimplementation, proximal section 33 has an OD of about 0.104 inches andan ID of about 0.088 inches. The distal section 34 has an OD of about0.085 inches and an ID of about 0.070 inches.

Diameters outside of the preferred ranges may also be used, providedthat the functional consequences of the diameter are acceptable for theintended purpose of the catheter. For example, the lower limit of thediameter for any portion of tubular body 16 in a given application willbe a function of the number of fluid or other functional lumen containedin the catheter, together with the acceptable minimum aspiration flowrate and collapse resistance.

Tubular body 16 must have sufficient structural integrity (e.g., columnstrength or “pushability”) to permit the catheter to be advanced todistal locations without buckling or undesirable bending of the tubularbody. The ability of the body 16 to transmit torque may also bedesirable, such as to avoid kinking upon rotation, to assist insteering. The tubular body 16, and particularly the distal section 34,may be provided with any of a variety of torque and/or column strengthenhancing structures. For example, axially extending stiffening wires,spiral wrapped support layers, braided or woven reinforcement filamentsmay be built into or layered on the tubular body 16. See, for example,U.S. Pat. No. 5,891,114 to Chien, et al., the disclosure of which isincorporated in its entirety herein by reference.

In many applications, the proximal section 33 will not be required totraverse particularly low profile or tortuous arteries. For example, theproximal section 33 will be mostly or entirely within the relativelylarge diameter guide catheter. The transition 32 can be located on thecatheter shaft 16 to correspond approximately with or beyond the distalend of the guide catheter.

For certain applications, such as intracranial catheterizations, thedistal section 34 is preferably at least about 5 cm or 10 cm long andsmall enough in diameter to pass through vessels as low as 3 mm or 2 mmor lower. The distal section may have a length of at least about 20 cmor 30 cm or 40 cm or more, depending upon the intended target vessel ortreatment site.

The distal section, whether carried within the proximal section as anintegrated device, or is a separate device to be inserted into theproximal section during a procedure, is substantially shorter than theproximal section. When the distal end of the distal section and thedistal end of the proximal section are axially aligned, the proximal endof the distal section is spaced distally apart from the proximal end ofthe proximal section. The control element such as a control wire or tubespans the distance between the proximal end of the distal section andthe proximal manifold or proximal control.

In the foregoing configuration, the proximal end of the distal sectionwill generally be spaced apart distally from the proximal end of theproximal section by at least about 25%, and in some embodiments at leastabout 50% or 70% or more of the length of the proximal section.

There is provided in according with one aspect, a telescoping catheter,comprising: an elongate, flexible tubular body, comprising a proximalsection having at least one lumen and a distal section axially movablypositioned within the lumen; and a control for advancing the distalsection from a first, proximally retracted position within the proximalsection to a second, extended position, extending distally beyond theproximal section; and an active tip on the distal end of the distalsection, comprising a distal opening that is movable between a smallerand a larger configuration.

In one aspect of present disclosure, the control comprises a pull wireextending through the proximal section. In another aspect of presentdisclosure, the distal section is distally advanceable to extend beyondthe proximal section for a distance of at least about 10 cm. In yetanother aspect of present disclosure, the distal section is distallyadvanceable to extend beyond the proximal section for a distance of atleast about 25 cm.

In one aspect of present disclosure, the distal opening is movable inresponse to movement of a control wire. In another aspect of presentdisclosure, the distal opening is movable between a smaller and a largerconfiguration in response to application of vacuum to the lumen. In yetanother aspect of present disclosure, the size of the distal opening ischanged by lateral movement of a side wall on the distal section. In yetanother aspect of present disclosure, the distal opening comprises atleast one movable jaw. In another aspect of present disclosure, thedistal end of the distal section comprises a duck bill valveconfiguration.

In one aspect of present disclosure, the telescoping catheter mayfurther comprise a controller for applying intermittent vacuum to thelumen. The controller may be configured to apply pulses of vacuum to thelumen spaced apart by spaces of neutral pressure. The controller may beconfigured to alternate between applying pulses of higher negativepressure and lower negative pressure. The distal tip of the catheter mayaxially reciprocate in response to application of pulses of vacuum tothe lumen.

In accordance with one aspect, there is provided a method of aspiratinga vascular occlusion from a remote site, comprising the steps of:advancing a first elongate tubular body through a vascular access siteand into a body vessel; thereafter advancing a second tubular bodydistally to extend beyond the first elongate tubular body to reach theremote site, the second tubular body having a lumen and a length that isshorter than the first elongate tubular body; and aspirating thrombusfrom the site into the lumen by applying pulsatile vacuum to the firstelongate tubular body.

In one aspect of present disclosure, the aspirating step comprisesbiting the thrombus by changing the size of a distal opening on thecatheter. The changing the size of the opening may be accomplished inresponse to application of intermittent vacuum to the lumen. In anotheraspect of present disclosure, the method of aspirating a vascularocclusion further comprises vibrating the first elongate tubular bodyduring the advancing a first elongate tubular body step. In yet anotheraspect of present disclosure, the method of aspirating a vascularocclusion further comprises vibrating the second tubular body during theadvancing a second tubular body step. In yet another aspect of presentdisclosure, the method of aspirating a vascular occlusion furthercomprises vibrating at least the distal section of the second tubularbody during the aspirating step.

In one aspect of present disclosure, the second tubular body has aproximal opening, and the proximal opening is positioned within thefirst elongate tubular body within about 25 cm of the distal end of thefirst elongate tubular body following the advancing the second tubularbody distally step. In another aspect of present disclosure, the secondtubular body is introduced into the first elongate tubular bodyfollowing the advancing the first elongate tubular body step. In yetanother aspect of present disclosure, the second tubular body is carriedwithin the first elongate tubular body during the advancing the firstelongate tubular body step.

In one aspect of present disclosure, the method of aspirating a vascularocclusion may further comprise advancing an agitator into the secondtubular body following the advancing a second tubular body step. Themethod of aspirating a vascular occlusion may further comprise rotatingthe agitator to assist the aspirating thrombus step. The method ofaspirating a vascular occlusion may further comprise introducing alubricant through the agitator to assist the aspirating thrombus step.More specifically, the method of aspirating a vascular occlusion mayfurther comprise introducing polyethylene glycol through the agitator toassist the aspirating thrombus step.

In one aspect of present disclosure, the aspirating thrombus stepcomprises applying intermittent negative pressure to the first elongatetubular body. In another aspect of present disclosure, the aspiratingthrombus step comprises applying alternating negative and positivepressure to the first elongate tubular body. In yet another aspect ofpresent disclosure, the advancing a second tubular body distally stepcomprises distally advancing a control wire extending proximally from aproximal end of the second tubular body. The control wire may betubular, and the method of aspirating a vascular occlusion may furthercomprise the step of advancing an agitator through the control wire suchthat a distal segment of the agitator is exposed beyond the control wireand within the second tubular body.

In accordance with one aspect, there is provided a system for aspiratinga vascular occlusion from a remote site, comprising: an elongate,flexible tubular body, comprising at least one central lumen extendingalong its longitudinal length; an agitator extendable through thecentral lumen of the tubular body to position a distal end of theagitator near a distal end of the tubular body; a driver connectable toa proximal end of the agitator and configured to actuate the agitator;and a vacuum port near the proximal end of the tubular body and in fluidcommunication with the central lumen of the tubular body.

In one aspect of present disclosure, the agitator comprises an elongatetube. The agitator may comprise a wire extending through the elongatetube and having at least one bend near its distal end. In another aspectof present disclosure, the agitator comprises a proximal end, a distalend, and a loop at the distal end. In yet another aspect of presentdisclosure, the driver is configured to rotate the agitator cyclicallyin alternating directions.

In one aspect of present disclosure, the agitator comprises: at leastone lumen along its longitudinal length, an influent port near itsproximal end configured to allow fluid communication between the lumenof the agitator and a source of media, and at least one effluent portconfigured to allow fluid communication between the lumen of theagitator and the central lumen of the tubular body. The system foraspirating a vascular occlusion may further comprise a control, forexpressing media from the effluent port of the agitator into the centrallumen of the tubular body. The distal portion of the tubular body may beconfigured to vibrate in a transverse direction in response to theinjection of media.

In one aspect of present disclosure, the system for aspirating avascular occlusion further comprises a controller for applying apulsatile vacuum cycle to the central lumen. In another aspect ofpresent disclosure, the system for aspirating a vascular occlusionfurther comprises a rotating hemostasis valve coupled to the proximalend of the tubular body, the rotating hemostasis valve comprising: atleast one main lumen along its longitudinal length, through which theproximal portion of the agitator is configured to pass, and anaspiration lumen bifurcating from the main lumen and provided with avacuum port. In yet another aspect of present disclosure, the systemfurther comprises a proximal drive assembly coupled to the proximal endof the tubular body, the proximal drive assembly comprising: at leastone main lumen along its longitudinal length for receiving the agitator;a media injection port, into which media is injected, in fluidcommunication with the central lumen of the tubular body, and a proximaldrive connection at the proximal end, which operably connects betweenthe agitator and the driver.

In accordance with another aspect, there is provided a method ofaspirating a vascular occlusion from a remote site, comprising:providing the system for aspirating a vascular occlusion; placing thetubular body adjacent to the occlusion; activating the driver to actuatethe agitator and loosen the occlusion; and drawing occlusive materialinto the central lumen by applying vacuum to the central lumen. In oneaspect of present disclosure, there is provided a method of aspirating avascular occlusion from a remote site, comprising: providing the systemfor aspirating a vascular occlusion; placing the tubular body adjacentto the occlusion; activating the driver to cause the distal tip of theagitator to rotate; injecting media through the influent port; andaspirating occlusive material into the central lumen by applying vacuumto the central lumen. Actuation of the driver, aspiration, and mediainjection may be synchronized to facilitate the removal and/oraspiration of the occlusion.

In accordance with one aspect, there is provided a method of aspiratinga vascular occlusion from a remote site, comprising: advancing aguidewire to a site at least as distal as the cavernous segment of theinternal carotid artery; advancing a tubular body directly over theguidewire to a site at least as distal as the cavernous segment;removing the guidewire from the tubular body; and aspirating thrombusinto the tubular body by applying vacuum to the tubular body. In oneaspect of present disclosure, the method of aspirating a vascularocclusion comprises advancing the tubular body at least as distal as thecerebral segment of the internal carotid artery. In another aspect ofpresent disclosure, the method of aspirating a vascular occlusioncomprises advancing the guidewire at least as distal as the middlecerebral artery.

In yet another aspect of present disclosure, the method of aspirating avascular occlusion further comprises providing sufficient back upsupport to the tubular body to resist prolapse of the tubular body intothe aorta. In one aspect, the back up support may be provided byadvancing the tubular body over a guidewire having a distal endpositioned at least as distal as the cavernous segment of the internalcarotid artery, and a diameter at the point the guidewire enters thebrachiocephalic artery of at least about 0.030 inches. In anotheraspect, the back up support may be provided by advancing the tubularbody over a guidewire having a distal end positioned at least as distalas the cavernous segment of the internal carotid artery, and a diameterat the point the guidewire enters the brachiocephalic artery of about0.038 inches. The guidewire may be navigable to at least the cerebralsegment of the internal carotid artery by having a distal segment havinga diameter of no more than about 0.020 inches. The guidewire may benavigable to at least the cerebral segment of the internal carotidartery by having a distal segment having a diameter of about 0.016inches. The distal segment may have a length of no more than about 25cm. The distal segment may have a length of no more than about 20 cm.

In accordance with another aspect, there is provided a method oftracking an aspiration catheter from a femoral access site to at leastas distal as the cavernous segment of the internal carotid artery,comprising the steps of: advancing a guidewire from the femoral accesssite to at least as distal as the cerebral segment of the internalcarotid artery, the guidewire having a proximal section having adiameter of at least about 0.030 inches and a distal section having alength of no more than about 25 cm and a diameter of no more than about0.020 inches; tracking an aspiration catheter directly over theguidewire and to a site at least as distal as the cavernous segment, theaspiration catheter having a distal end and a central lumen at thedistal end with a diameter of at least about 0.080 inches and a beveleddistal tip. In one aspect of present disclosure, the diameter of theproximal section of the guidewire is about 0.038 inches, and thediameter of the distal section is about 0.016 inches.

In another aspect of present disclosure, a distal segment of thecatheter comprises a side wall defining the central lumen, the side wallcomprising: a tubular inner liner; a soft tie layer separated from thelumen by the inner liner; a helical coil surrounding the tie layer,adjacent windings of the coil spaced progressively further apart in thedistal direction; and an outer jacket surrounding the helical coil, theouter jacket formed from a plurality of tubular segments positionedcoaxially about the coil; wherein a proximal one of the tubular segmentshas a durometer of at least about 60 D and a distal one of the tubularsegments has a durometer of no more than about 35 D. The tubular linermay be formed by dip coating a removable mandrel and may comprise PTFE.The tie layer may comprise polyurethane. The tie layer may have a wallthickness of no more than about 0.005 inches and may extend along atleast the most distal 20 cm of the flexible body. The coil may comprisea shape memory material.

In accordance with one aspect, there is provided an enhanced flexibilityneurovascular catheter, comprising: an elongate flexible body, having aproximal end, a distal end and a side wall defining a central lumen, adistal zone of the side wall comprising: an outer jacket surrounding ahelical coil, the outer jacket formed from a plurality of tubularsegments positioned coaxially about the coil; wherein a proximal one ofthe tubular segments has a durometer of at least about 60 D and a distalone of the tubular segments has a durometer of no more than about 35 D;and an axially extending filament within the side wall, extending atleast about the most distal 10 cm of the length of the catheter. Thefilament may extend at least about the most distal 15 cm of the lengthof the catheter. The filament may extend at least about the most distal20 cm of the length of the catheter. The filament may comprise multiplefibers and may extend axially in between the coil and the inner liner.

In one aspect of present disclosure, the side wall further comprises: atubular inner liner; a soft tie layer separated from the lumen by theinner liner; wherein the helical coil surrounds the tie layer, andadjacent windings of the coil are spaced progressively further apart inthe distal direction. The tubular liner may be formed by dip coating aremovable mandrel and may comprise PTFE. The tie layer may comprisepolyurethane and may have a wall thickness of no more than about 0.005inches. The tie layer may extend along at least the most distal 20 cm ofthe flexible body. The coil may comprise a shape memory material and maycomprise Nitinol. The Nitinol may comprise an Austenite state at bodytemperature.

In one aspect of present disclosure, the outer jacket may be formed fromat least five discrete tubular segments. In another aspect of presentdisclosure, the outer jacket may be formed from at least nine discretetubular segments. The difference in durometer between a proximal one ofthe tubular segments and a distal one of the tubular segments may be atleast about 20 D. The difference in durometer between a proximal one ofthe tubular segments and a distal one of the tubular segments may be atleast about 30 D. In another aspect of present disclosure, the cathetercan withstand at least about 3.5 pounds tension before failure. In yetanother aspect, the catheter can withstand at least about 5 poundstension before failure.

In accordance with one aspect, there is provided a method of making ahigh flexibility distal zone on a neurovascular catheter, comprising thesteps of: dip coating a removable mandrel to form a tubular inner layeron the mandrel; coating the tubular inner layer with a soft tie layer;applying a helical coil to the outside of the tie layer; positioning aplurality of tubular segments on the helical coil; the plurality ofsegments having durometers that decrease in a distal direction; heatingthe tubular segments to form the high flexibility distal zone on theneurovascular catheter; and removing the mandrel. In one aspect ofpresent disclosure, removing the mandrel step includes axiallyelongating the mandrel. In another aspect of present disclosure, themethod of making a high flexibility distal zone on a neurovascularcatheter comprises positioning at least seven segments on the helicalcoil. In yet another aspect of present disclosure, the method of makinga high flexibility distal zone on a neurovascular catheter comprisespositioning at least nine segments on the helical coil.

In one aspect of present disclosure, the difference in durometer betweena proximal one of the tubular segments and a distal one of the tubularsegments is at least about 20 D. The difference in durometer between aproximal one of the tubular segments and a distal one of the tubularsegments may be at least about 30 D. The tubular inner layer maycomprise PTFE. In another aspect of present disclosure, the tie layercomprises polyurethane. The tie layer may have a wall thickness of nomore than about 0.005 inches. The tie layer may extend along at leastthe most distal 20 cm of the flexible body.

In one aspect of present disclosure, the coil comprises a shape memorymaterial. The coil may comprise Nitinol. The Nitinol may comprise anAustenite state at body temperature. In another aspect of presentdisclosure, the method of making a high flexibility distal zone on aneurovascular catheter further comprises the step of positioning atleast one tensile strength enhancing filament in between the coil andthe tie layer prior to heat shrinking the tubular segments. The filamentmay extend along at least about the most distal 15 cm of the length ofthe catheter. The filament may extend along at least about the mostdistal 20 cm of the length of the catheter. The filament may comprisemultiple fibers. In yet another aspect of present disclosure, the methodof making a high flexibility distal zone on a neurovascular catheterfurther comprises the step of positioning at least one tensile strengthenhancing filament over the tie layer before the applying a helical coilstep.

In accordance with one aspect, there is provided a method of aspiratinga vascular occlusion from a remote site, comprising the steps of:advancing an elongate tubular body through a vascular access site andinto a body vessel, the tubular body comprising a proximal end, a distalend and a central lumen; positioning the distal end at least as fardistally as the cavernous segment of the middle cerebral artery;applying vacuum to the lumen to draw thrombus into the lumen; andmechanically disrupting the thrombus to facilitate entry into the lumen.

In one aspect of present disclosure, the mechanically disrupting stepcomprises introducing vibration at the distal end of the tubular body.The vibration may be introduced by rotating an agitator within thetubular body. The method of aspirating a vascular occlusion may compriserotating a wire within the tubular body. The method of aspirating avascular occlusion may comprise rotating a tube within the tubular bodyand may further comprise the step of introducing media through the tube.The method of aspirating a vascular occlusion may comprise the step ofintroducing a lubricant through the tube to facilitate advancingthrombus through the lumen and may comprise the step of introducingpolyethylene glycol through the tube.

In another aspect of present disclosure, the applying vacuum stepcomprises applying pulsatile vacuum. In yet another aspect of presentdisclosure, the advancing an elongate tubular body step is accomplisheddirectly over a guidewire without any intervening tubular bodies. Themethod of aspirating a vascular occlusion may comprise advancing thetubular body at least as distal as the cavernous segment of the internalcarotid artery. The method of aspirating a vascular occlusion maycomprise advancing the tubular body at least as distal as the cerebralsegment of the internal carotid artery. The method of aspirating avascular occlusion may comprise advancing the guidewire at least asdistal as the middle cerebral artery.

In one aspect of present disclosure, the method of aspirating a vascularocclusion further comprises providing sufficient back up support to thetubular body to resist prolapse of the tubular body into the aorta. Theback up support may be provided to the tubular body by advancing thetubular body over a guidewire having a distal end positioned at least asdistal as the cavernous segment of the internal carotid artery, and adiameter at the point the guidewire enters the brachiocephalic artery ofat least about 0.030 inches. The back up support may be provided to thetubular body by advancing the tubular body over a guidewire having adistal end positioned at least as distal as the cavernous segment of theinternal carotid artery, and a diameter at the point the guidewireenters the brachiocephalic artery of about 0.038 inches.

In one aspect of present disclosure, the guidewire is navigable to atleast the cerebral segment of the internal carotid artery by having adistal segment having a diameter of no more than about 0.020 inches. Theguidewire may be navigable to at least the cerebral segment of theinternal carotid artery by having a distal segment having a diameter ofabout 0.016 inches. In yet another aspect of present disclosure, themethod of aspirating a vascular occlusion further comprises the step ofintroducing an agitator into the tubular body subsequent to thepositioning step. A proximal section of the agitator may extend througha constraint tube, and a distal section of the agitator may extendbeyond a distal end of the constraint tube.

In accordance with one aspect, there is provided a method of aspiratinga vascular occlusion from a remote site, comprising: advancing aguidewire through a vascular access point and transvascularly to a siteat least as distal as the cavernous segment of the internal carotidartery; accessing a site at least as distal as the cavernous segment byadvancing a combined access and aspiration catheter directly over theguidewire; removing the guidewire; and aspirating thrombus through thecombined access and aspiration catheter. In one aspect of presentdisclosure, the method of aspirating a vascular occlusion comprisesadvancing the combined access and aspiration catheter at least as distalas the cerebral segment of the internal carotid artery. In anotheraspect of present disclosure, the method of aspirating a vascularocclusion comprises advancing the guidewire at least as distal as themiddle cerebral artery.

In yet another aspect of present disclosure, the method of aspirating avascular occlusion further comprises providing sufficient back upsupport to the combined access and aspiration catheter to resistprolapse of the catheter into the aorta. The back up support may beprovided to the combined access and aspiration catheter by advancing thecombined access and aspiration catheter over a guidewire having a distalend positioned at least as distal as the cavernous segment of theinternal carotid artery, and a diameter at the point the guidewireenters the brachiocephalic artery of at least about 0.030 inches. Theback up support is provided to the combined access and aspirationcatheter by advancing the combined access and aspiration catheter over aguidewire having a distal end positioned at least as distal as thecavernous segment of the internal carotid artery, and a diameter at thepoint the guidewire enters the brachiocephalic artery of about 0.038inches.

In one aspect of present disclosure, the guidewire is navigable to atleast the cerebral segment of the internal carotid artery by having adistal segment having a diameter of no more than about 0.020 inches. Theguidewire may be navigable to at least the cerebral segment of theinternal carotid artery by having a distal segment having a diameter ofabout 0.016 inches. The diameter of the proximal section of theguidewire may be about 0.038 inches, and the diameter of the distalsection may be about 0.016 inches.

In another aspect of present disclosure, a distal segment of thecombined access and aspiration catheter comprises a side wall defining acentral lumen, the side wall comprising: a tubular inner liner; a tielayer separated from the lumen by the inner liner; a helical coilsurrounding the tie layer, adjacent windings of the coil spacedprogressively further apart in the distal direction; and an outer jacketsurrounding the helical coil, the outer jacket formed from a pluralityof tubular segments positioned coaxially about the coil; wherein aproximal one of the tubular segments has a durometer of at least about60 D and a distal one of the tubular segments has a durometer of no morethan about 35 D. The tubular liner may be formed by dip coating aremovable mandrel. The tubular liner may comprise PTFE. The tie layermay comprise polyurethane, and may have a wall thickness of no more thanabout 0.005 inches. The tie layer may extend along at least the mostdistal 20 cm of the flexible body.

In one aspect of present disclosure, the coil comprises a shape memorymaterial. In another aspect of present disclosure, the method ofaspirating a vascular occlusion further comprises introducing anagitator into the combined access and aspiration catheter. The method ofaspirating a vascular occlusion may further comprise vibrating a distalportion of the agitator during the aspirating step. The method ofaspirating a vascular occlusion may further comprise introducing a fluidmedia through the agitator during the aspirating step. The method ofaspirating a vascular occlusion may further comprise introducingpolyethylene glycol through the agitator during the aspirating step.

In accordance with one aspect, there is provided a neurovascularcatheter, comprising: an elongate flexible tubular body, having aproximal end, a distal end and a side wall defining a central lumen, adistal zone of the tubular body comprising: a tubular inner liner; a tielayer separated from the lumen by the inner liner; a helical coilsurrounding the tie layer, adjacent windings of the coil spacedprogressively further apart in the distal direction; an outer jacketsurrounding the helical coil, and an opening at the distal end which isenlargeable from a first inside diameter for transluminal navigation toa second, larger inside diameter to facilitate aspiration of thrombusinto the lumen. In one aspect of present disclosure, the distal openingis enlargeable in response to exposure to blood. In another aspect ofpresent disclosure, the distal opening is enlargeable in response toexposure to body temperature. In yet another aspect of presentdisclosure, the distal opening is enlargeable in response to removal ofa constraint. The constraint may comprise a polymer having a structuralintegrity that decreases in the intravascular environment.

In one aspect of present disclosure, the catheter body adjacent thedistal opening comprises a radially outwardly biased embedded support.The catheter body adjacent the distal opening may comprise an embeddedNitinol frame. The support may comprise a wire mesh. The support maycomprise a stent. In another aspect of present disclosure, the catheterbody adjacent the distal opening comprises a hydrophilic blend. In yetanother aspect of present disclosure, the tubular liner is formed by dipcoating a removable mandrel. The tubular liner may comprise PTFE.

In one aspect of present disclosure, the tie layer comprisespolyurethane. The tie layer may have a wall thickness of no more thanabout 0.005 inches. The tie layer may extend along at least the mostdistal 20 cm of the flexible body. In another aspect of presentdisclosure, the coil comprises a shape memory material. The coil maycomprise Nitinol. The Nitinol may comprise an Austenite state at bodytemperature. In one aspect of present disclosure, the outer jacket isformed from at least five discrete tubular segments. The outer jacketmay be formed from at least nine discrete tubular segments. Thedifference in durometer between a proximal one of the tubular segmentsand a distal one of the tubular segments may be at least about 20 D. Thedifference in durometer between a proximal one of the tubular segmentsand a distal one of the tubular segments may be at least about 30 D.

In accordance with one aspect, there is provided a neurovascularcatheter extension segment, comprising: an elongate flexible controlwire, having a proximal end and a distal end; a tubular extensionsegment having a side wall defining a central lumen carried by thedistal end of the control wire, the side wall comprising: a tubularinner liner; a tie layer separated from the lumen by the inner liner; ahelical coil surrounding the tie layer; and an outer jacket surroundingthe helical coil. In one aspect of present disclosure, the outer jacketis formed from a plurality of tubular segments positioned coaxiallyabout the coil. A proximal one of the tubular segments may have adurometer of at least about 60 D, and a distal one of the tubularsegments may have a durometer of no more than about 35 D.

In another aspect of present disclosure, the tubular liner is formed bydip coating a removable mandrel. The tubular liner may comprise PTFE. Inyet another aspect of present disclosure, the tie layer comprisespolyurethane. The tie layer may have a wall thickness of no more thanabout 0.005 inches. The tie layer may extend along at least the mostdistal 20 cm of the tubular extension segment. In one aspect of presentdisclosure, the coil comprises a shape memory material. The coil maycomprise Nitinol. The Nitinol may comprise an Austenite state at bodytemperature.

In one aspect of present disclosure, the outer jacket is formed from atleast five discrete tubular segments. The outer jacket may be formedfrom at least nine discrete tubular segments. The difference indurometer between a proximal one of the tubular segments and a distalone of the tubular segments may be at least about 20 D. The differencein durometer between a proximal one of the tubular segments and a distalone of the tubular segments may be at least about 30 D. In anotheraspect of present disclosure, the control wire comprises a centrallumen. The control wire central lumen may be in communication with thecentral lumen of the tubular extension segment. In yet another aspect ofpresent disclosure, the inside diameter of the neurovascular catheterextension segment is at least 2× the inside diameter of the control wirecentral lumen. The inside diameter of the neurovascular catheterextension segment may be at least 3× the inside diameter of the controlwire central lumen.

In accordance with another aspect, there is provided a neurovascularcatheter extension segment system, comprising the neurovascular catheterextension segment described above and an agitator configured to extendthrough the control wire central lumen and into the central lumen of thetubular extension segment.

Although the present invention has been described in terms of certainpreferred embodiments, it may be incorporated into other embodiments bypersons of skill in the art in view of the disclosure herein. The scopeof the invention is therefore not intended to be limited by the specificembodiments disclosed herein, but is intended to be defined by the fullscope of the following claims.

What is claimed is:
 1. An enhanced flexibility neurovascular catheter,comprising: an elongate flexible body, having a proximal end, a distalend, a side wall defining a central lumen, and a proximal zone and adistal zone being separated by a transition region extending from theproximal zone to the distal zone, the side wall comprising: a tubularinner liner; a tie layer separated from the lumen by the inner liner; ahelical coil surrounding the tie layer and extending a length from thedistal end of at least about 20% of the length of the elongate flexiblebody, the length less than or equal to a length of the distal zone,adjacent windings of the coil spaced progressively further apart in thedistal direction; a tubular braid surrounding the inner liner, thetubular braid being proximal to the helical coil; and an outer jacketsurrounding the helical coil and the tubular braid, the outer jackethaving a durometer of no more than about 35 D along the entire length ofthe distal zone and a durometer of at least about 60 D along an entirelength of the proximal zone; wherein the outer jacket is formed alongthe transition region from a plurality of tubular segments, the tubularsegments each having a durometer between the durometer of the outerjacket along the proximal zone and the durometer of the outer jacketalong the distal zone, each of the durometers decreasing in the distaldirection, the transition region being no longer than about 5 cm.
 2. Anenhanced flexibility neurovascular catheter as in claim 1, wherein thetubular inner liner is formed by dip coating a removable mandrel.
 3. Anenhanced flexibility neurovascular catheter as in claim 1, wherein thetubular inner liner comprises polytetrafluoroethylene.
 4. An enhancedflexibility neurovascular catheter as in claim 1, wherein the tie layercomprises polyurethane.
 5. An enhanced flexibility neurovascularcatheter as in claim 4, wherein the tie layer has a wall thickness of nomore than about 0.005 inches.
 6. An enhanced flexibility neurovascularcatheter as in claim 4, wherein the tie layer extends along at least themost distal 20 cm of the flexible body.
 7. An enhanced flexibilityneurovascular catheter as in claim 1, wherein the coil comprises a shapememory material.
 8. An enhanced flexibility neurovascular catheter as inclaim 7, wherein the coil comprises Nitinol.
 9. An enhanced flexibilityneurovascular catheter as in claim 8, wherein the Nitinol comprises anAustenite state at body temperature.
 10. An enhanced flexibilityneurovascular catheter as in claim 1, wherein the outer jacket over thetransition region and the distal zone is formed from at least fivediscrete tubular segments.
 11. An enhanced flexibility neurovascularcatheter as in claim 1, wherein the outer jacket over the transitionregion and the distal zone is formed from at least nine discrete tubularsegments.
 12. An enhanced flexibility neurovascular catheter as in claim11, wherein the difference in durometer between a proximal one of thetubular segments and a distal one of the tubular segments of the outerjacket over the transition region and the distal zone is at least about20 D.
 13. An enhanced flexibility neurovascular catheter as in claim 11,wherein the difference in durometer between a proximal one of thetubular segments and a distal one of the tubular segments of the outerjacket over the transition region and the distal zone is at least about30 D.
 14. An enhanced flexibility neurovascular catheter as in claim 1,further comprising a tension support for increasing the tensionresistance in the distal zone.
 15. An enhanced flexibility neurovascularcatheter as in claim 14, wherein the tension support comprises afilament.
 16. An enhanced flexibility neurovascular catheter as in claim1, wherein the outer jacket comprises at least three tubular segmentsalong the transition region.
 17. An enhanced flexibility neurovascularcatheter as in claim 1, wherein the elongate flexible body comprises aconstant outer diameter along the length of the transition region. 18.An enhanced flexibility neurovascular catheter as in claim 1, whereinthe distal zone comprises a smaller outer diameter than the proximalzone.
 19. An enhanced flexibility neurovascular catheter, comprising: anelongate flexible body, having a proximal end, a distal end and a sidewall defining a central lumen, the sidewall comprising: a tubular innerliner; a tie layer separated from the lumen by the inner liner; ahelical coil surrounding the tie layer; and an outer jacket surroundingthe helical coil, the outer jacket formed from a plurality of tubularsegments positioned coaxially about the coil; wherein a proximal zoneand a distal zone of the flexible body are separated by a transitionregion extending from the proximal zone to the distal zone, the proximalzone comprising a durometer of at least about 60 D along an entirelength of the proximal zone; the distal zone comprising a durometer ofno more than about 35 D along an entire length of the distal zone, thelength being at least about 15 cm; and the transition region comprisingat least two of the plurality of tubular segments, the at least twosegments having durometers between the durometer of the proximal zoneand the durometer of the distal zone and which decrease in the distaldirection, the transition region being no longer than about 5 cm.
 20. Anenhanced flexibility neurovascular catheter as in claim 19, wherein thelength of the distal zone is at least about 20 cm.